16-Aryloxy-17,18,19,20-tetranorprostanoic acids and derivatives

ABSTRACT

This disclosure describes novel 16-aryloxy-17,18,19,20-tetranoprostanoic acids and derivatives thereof useful as bronchodilators and as hypotensive and contraceptive agents.

This is a continuation, of application Ser. No. 748,976 filed Dec. 9,1976.

BRIEF SUMMARY OF THE INVENTION

This invention relates to novel16-aryloxy-17,18,19,20-tetranorprostanoic acids, their derivatives andintermediates for preparing same. More specifically the novel compoundsof this invention can be represented by the following two generalformulae wherein A has the same absolute configuration as is found inthe naturally-occurring mammallian prostaglandins, and all theracemates, racemic mixtures and diasteromeric mixtures thereof. ##STR1##wherein R₁ is hydroxy or an alkoxy group having from one to twelvecarbon atoms; R₂ is a phenyl, benzyl, naphthyl, or5,6,7,8-tetrahydronaphthyl group optionally substituted with one or twoof the following groups: halogen, lower alkyl, lower alkoxy, ortrifluoromethyl radicals; n is an integer having the value 2 to 4,inclusive; Y is a divalent radical selected from the group consisting of##STR2## X is a divalent radical selected from the group consisting of##STR3## C₅ -C₆ is ethylene or cis-vinylene; C₁₃ -C₁₄ is ethylene ortrans-vinylene; with the proviso that when C₅ -C₆ is cis-vinylene thenC₁₃ -C₁₄ is trans-vinylene.

When X is ##STR4## it represents the 15α-hydroxy derivative, and the15β-hydroxy derivatives when it is ##STR5##

Suitable lower alkyl and lower alkoxy groups contemplated by the presentinvention are those having up to four carbon atoms such as, for example,methyl, propyl, iso-propyl, n-butyl, sec-butyl, methoxy, ethoxy,t-butoxy, etc.

Also embraced within the scope of the present invention are thenon-toxic, pharmaceutically acceptable salts of the novel compounds ofthe present invention when R₁ is hydroxy. The cations comprised in thesesalts include, for example, the non-toxic metal cations such as thesodium ion, potassium ion, calcium ion, and magnesium ion as well as theorganic amine cations such as the tri(lower alkyl)amine cations (e.g.,triethylamine), procaine, and the like.

The novel compounds of the present invention are obtainable as yellowoils or crystalline solids having characteristics absorption spectra.They are relatively insoluble in water but are relatively soluble incommon organic solvents such as ethanol, ethyl acetate,dimethylformamide, and the like. The cationic salts of the compoundswhen R₁ is hydroxy are, in general, white to yellow crystalline solidshaving characteristic absorption spectra. They are relatively soluble inwater, methanol and ethanol but are relatively insoluble in benzene,diethyl ether, and petroleum ether.

DETAILED DESCRIPTION OF THE INVENTION

The prostaglandins are a family of closely related compounds which havebeen obtained from various animal tissues, and which stimulate smoothmuscle, lower arterial blood pressure, antagonize epinephrine-inducedmobilization of free fatty acids, and have other pharmacological andautopharmacological effects in mammals. See Bergstom et al., J. Biol.Chem., 238, 3555 (1963) and Horton, Experienta, 21, 113 (1965) andreferences cited therein. All of the so-called natural prostaglandinsare derivatives of prostanoic acid. ##STR6## The hydrogen atoms attachedto C-8 and C-12 are in trans configuration. The natural prostaglandinsrepresent only one of the possible optical isomers. The compounds ofthis convention include all possible optical isomers.

The novel compounds of this invention are prepared from thecorresponding known 11α-hydroxy-9-oxo-5-cis,13-trans-prostadienoic acids(I) (Netherlands Patent No. 7,206,361; November 14, 1972) as illustratedin Flowsheet A which follows and in which n, R₂ and C₅ -C₆ are ashereinabove defined and in which THP is the tetrahydropyranyl group.##STR7##

According to Flowsheet A above, dehydration of (I) in the usual mannerprovides the16-aryloxy-15α-hydroxy-9-oxo-17,20-tetranor-5-cis,10,13-trans-prostatrienoicacids (III) which upon treatment with dihydropyran and acid provide thebistetrahydropyranyl derivative (V). Upon treatment of (V) with sodiumborohydride or sodium cyanoborohydride (pH 3-4), a mixture (VII) of9α,15α-dihydroxy-16-aryloxy-9-oxo-17,20-tetranor-5-cis,13-trans-prostadienoicacid and the corresponding 9α-hydroxyl prostadienoic acid is obtained.Oxidation of the 9-hydroxy mixture (VII) provides, after acidichydrolysis of the tetrahydropyranyl functions, the16-aryloxy-15α-hydroxy-9-oxo-17,20-tetranor-5-cis,13-trans-prostadienoicacid (VIII), which upon hydrogenation provides the fully saturated16-aryloxy-15α-hydroxy-9-oxo-17,20-tetranorprostanoic acids (IX).

Treatment of the16-aryloxy-11α,15α-dihydroxy-17,20-tetranor-5-cis,13-trans-prostadienoicacids (I) with dihydropyran and an acid catalyst provides thetris-tetrahydropyranyl derivatives (II) which can be selectively reducedat the C₅ -C₆ cis double bond. Acid-catalyzed hydrolysis of thetetrahydropyranyl moieties then provides the11α,15α-dihydroxy-9-oxo-16-aryloxy-17,20-tetranor-13-trans-prostenoicacids (IV), which when subjected to the steps as described above forI→III→V→VII→VIII provides the15α-hydroxy-9-oxo-16-aryloxy-17,20-tetranor-13-trans-prostenoic acids ofthis invention.

The 9-hydroxy derivative of this invention can also be obtained byreduction of the corresponding 9-oxo derivative. When the reduction iscarried out in the usual manner with sodium borohydride in ethanol assolvent, the product is a mixture of the 9α- and 9β-hydroxy derivative(X) and (XI), respectively. These isomers are separable bychromatographic procedures. The stereoselective preparation of the9α-hydroxy derivative (X) can be accomplished by reduction of the 9-oxoderivative with either lithium perhydro-9b-borophenalyl hydride [H. C.Brown and W. C. Dickason, Jour. Amer. Chem. Soc., 92, 709 (1970)] orwith lithium tri-sec-butylborohydride. ##STR8##

The carboxylic acid esters (R₁ =alkoxy) of this invention can beprepared by treating the corresponding carboxylic acid with theappropriate diazoalkane by the usual procedures well known to the art.An alternative procedure involves blocking the 15-hydroxy function witha tetrahydropyranyl group, conversion of the carboxylic acid to an acidchloride and reacting with the appropriate alcohol in the presence of anacid-acceptor and deblocking.

All of the compounds of this invention can be isolated and purified byconventional methods. Isolation can be accomplished, for example, bydilution of the reaction mixture with water, extraction with awater-immiscible solvent such as methylene chloride, ethyl acetate,benzene, cyclohexane, ether, toluene and the like, chromatography,adsorption on ion-exchange resins, distillation, or a combination ofthese. Purification of the compounds of this invention can beaccomplished by means known in the art for the purification ofprostaglandins and lipids, fatty acids, and fatty esters. For example,partition chromatography, reverse phase partition chromatography,countercurrent distribution, adsorption chromatography on acid washedFlorisil® (synthetic magnesium silicate) and acid washed silica gel, drycolumn chromatography, preparative paper chromatography, preparativethin layer chromatography, chromatography over sili-ca loaded cationexchange resins, and combinations thereof can be used effectively topurify the compounds produced by the presence of this invention.

If a compound of this invention is prepared from a prostaglandin A (III,V, VI) which is in the optically active resolved from, then the productwill also be in the resolved form. On the other hand, if theprostaglandin A is racemic, the product will be racemic.

In formulae XII-XXIII, which follow, R₂, n, X, C₅ -C₆ and C₁₃ -C₁₄ areas hereinabove defined.

The racemic products and intermediates of this invention may be resolvedinto their optically active components by a number of methods ofresolution well known in the art. For example, the free carboxylic acidscan be treated with an optically active base such as cinchonine,quinine, brucine, d- or l-α-phenylethylamine and the like to producediastereoisomeric salts which can be separated by crystallization.Alternatively, the acid may be esterified with an optically activealcohol, e.g., d- or l-menthol, estradiol 3-acetate, etc., and thediastereoisomeric esters then resolved.

Resolution of the racemic prostaglandin-like compounds of this inventionmay also be accomplished by reverse phase and absorption chromatographyon an optically active support and adsorbent and by selectivetransformation of one isomer with a biologically-active prostaglanintransforming system. Such transformations can be carried out byincubation or perfusion, using methods well established in the art,followed by isolation and recovery of the isomer resistant to themetabolic transformation applied.

Additional procedures for effecting the resolution of the racemicproducts of this invention involve conversion of a 9α-hydroxy racemate(illustrated by XII and XIII below) to the corresponding hemiphthalate(e.g., XIV) and conversion of this diacid to a bis salt (e.g., XV) withan optically active amine (e.g., l-(-)-α-methylbenzylamine,d-(+)-α-methylbenzylamine, brucine, dehydroabietylamine, styrchnine,quinine, cinchonine, cinchonidine, quinidine, ephedrine, deoxyephedrine,amphetamine, (+)-2-amino-1-butanol (-)-2-amino-1-butanol and the like).The resulting diastereoisomers are then separated by fractionalcrystallization and the individual components are then converted byacidification and saponification to the individual optically activeparent 9α-hydroxy enantiomers (XII) and (XIII), oxidation of whichprovides the corresponding individual 9-oxo enantiomers (XVI) and(XVII). ##STR9##

Another procedure involves conversion of the 9α-hydroxy racemate (as the15-hydroxy blocked and then deblocked prostenoic acid ester) to thediastereomeric carbamates with an optically active isocyanate, e.g.,(+)-1-phenylethylisocyanate and (-)-1-phenylethylisocyanate. Separationof the diastereomers, for example, (XVIII) and (XIX), can beaccomplished by fractional crystallization or by the usualchromatographic procedures, or if necessary by high speed liquidchromatography involving, if required, recycling techniques [See G.Fallick, American Laboratory, 19-27 (August, 1973) as well as referencescited therein. Additional information concerning high speed liquidchromatography and the instruments necessary for its application isavailable from Waters Associates, Inc., Maple St., Milford, Mass.]Base-treatment of the individual diastereomeric carbamates then affordsthe individual enantiomeric alcohols. ##STR10##

It is also possible to effect resolution of the 9α-hydroxy racemate,preferably as the prostenoate ester, by esterification of the 9α-hydroxyfunction (15-hydroxy function blocked as a tetrahydropyranyl ether ortrimethylsilyl ester and then deblocked after 9α-hydroxyfunctionallyaction) with an optically active acid, via its acid chloride. Suitableoptically active acids include ωcamphoric acid, menthoxyacetic acid,3β-acetoxy-Δ⁵ -etianic acid, (-)-α-methoxy-S-trifluoromethylphenylacetic acid and (+)-α-methoxy-α-trifluoromethylphenylacetic acid, andthe like. The resulting diastereoisomeric esters, for example (XX) and(XXI) are then separated by fractional crystallization or bychromatographic techniques including if necessary, the use of high speedliquid chromatography. Saponification of the individual diastereoisomersthen provides the individual 9α-hydroxyprostenoic acid enantiomers (XII)and (XIII). ##STR11##

Another resolution procedure involves derivatization of the ketofunction of the racemic 9-oxoprostenoic acid or ester with the usualtype of ketone derivacizing agents bearing an optically active center.The resulting mixture of diastereomeric derivatives can then beseparated by fractional crystallization or by chromatography or, ifnecessary, by high speed liquid chromatography. The individualdiastereomeric keto derivatives, for example, (XXII) and (XXIII), arethen convertable to the individual 9-oxo enantiomers (XVI) and (XVII) byany of the usual cleavage techniques. Ketone reduction of the9-oxo-enantiomer as described hereinabove then provides thecorresponding 9α-hydroxy or 9β-hydroxy enantiomer. Among the opticallyactive reagents useful for ketone derivatization are1-α-aminoxy-γ-methylpentanoic acid hydrochloride [E. Testa et al., Helv.Chimica Acta, 47 (3), 766 (1973), menthylhydrazine, and4-α-methylbenzylisemicarbazide. ##STR12##

Other useful keto derivatizing agents are optically active 1,2-glycols,e.g., D(-)-2,3-butanediol, [for pertinent literature see, A. C. Neish,Can. Jour. Res. 23 sec. B, 10 (1945); G. E. Ward et al., Jour. Amer.Chem. Soc., 66, 541 (1944); J. Casanova, Jr. and E. J. Corey, Chem. andInd. (London), 1961, 1664)] or optically active dithiols, e.g.,L(+)-2,3-butanedithiol [see also E. J. Corey and R. B. Miha, Jour. Amer.Chem. Soc., 84, 2938 (1962)].

The novel compounds of this invention are useful as hypotensive agents(9-oxo-derivatives), bronchodilators for the treatment of asthma and asagents for the control of reproduction in females, in humans as well asin warm-blooded animals such as cattle, sheep, swine, horses, dogs andcats. Among the potential uses in domestic animals is thesynchronization of oestrus in cattle and other domestic animals, and theinduction of twinning.

In humans these compounds may have use as agents for the induction oflabor at term, as abortifacients and as menses inducers.

There are several possibilities of contraceptive attack during thenormal processes of mammalian female reproduction. These include anyothers ovulation blockage, interference with the fertilization of theovum by sperm, interference with the normal transport of ova and orzygotes in the reproductive tract, prevention of embryo implantation,disruption of the maternal response to embryonic implantation, andmaternal failure to support embryonic survival. While the exactmechanism or mechanisms which take place with the active ingredients ineffecting contraception is not clear, the compounds of this inventionmay prevent conception by one or more of the above-mentionedoccurrences. It is not intended, however, that the present invention belimited to any particular theory as to mechanism of contraception.

A major problem in the clinical use of prostaglandin E₂ andprostaglandin F₂ α, and indeed of prostaglandins of the 11α-hydroxyseries in general, is the often high incidence of gastrointestinalside-effects as manifested by nausea, vomiting and diarrhea. Presumably,these effects result from the stimulation of gastrointestinal smoothmuscle by the administered prostaglandin. One important advantage of thecompounds of this invention is that although they retain to asignificant extent the antifertility pot-ency of the parent 11-hydroxycompounds they show a highly diminished ability to stimulate smoothmuscle. This very significant and unanticipated separation of biologicaleffects suggests that the compounds of this invention have the potentialto be useful anti-fertility agents with a minimum of adverseside-effects. It is also conceivable that this separation will allow theuse of higher relative doses of these compounds than hitherto possiblewith the established prostaglandins. This also denotes the possibilitiesof more effective application in the field of post-conception control,e.g. inducing menses during approximately the first two weeks followingthe first missed menstruation. For a discussion of these problems seeToppozada et al. "Prostaglandins in Fertility Control" 3, 108 (1973),Report from Meetings of the Prostaglandin Task Force Steering Committeesponsored by the World Health Organization; and Wiqvist et al., ibid. 3,83 (1973).

The invention will be described in greater detail in conjunction withthe following specific examples.

EXAMPLE 1 Preparation ofd,l-11α,15α-dihydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis-13-trans-prostadienoicacid

A mixture of the 15 epimers ofdl-16-phenoxy-9α,11α,-15-trihydroxy-17,20-tetranor-5-cis-13-trans-prostadienoicacid is prepared in accordance with Netherlands Patent No. 7,206,361,page 9, Example 1. The two epimers are separated by the procedure ofNetherlands Patent No. 7,206,361, page 9, Example 1. The high Rfmaterial is assigned the 15β configuration and the low Rf material isassigned the 15α-configuration.dl-16-Phenoxy-9α,11α,15-trihydroxy-17,20-tetranor-5-cis-13-trans-prostadienoicacid (100 mg.) is dissolved in 2.0 ml. of dry acetone and stirred at-40° C. under argon, N-trimethylsilyldimethylamine (3 ml.) is then addedand after 1 hour the reaction is diluted with cold ether and extractedwith 50% saturated aqueous sodium bicarbonate. Evaporation to dryness invacuo yields as the major product:dl-11α,15α-bistrimethylsiloxy-9α-hydroxy-16-phenoxy-17,20-tetranor-5-cis-13-trans-prostadienoicacid trimethylsilyl ester.

The crude material is oxidized with Collins reagent (prepared in situfrom 170 mg. of chromic anhydride and 275 ml. of pyridine in 4 ml. ofmethylene chloride) for 5 minutes at 25° C. The reaction mixture isdiluted with ether and extracted with 0.5 M hydrochloric acid washedwith brine. The organic solution is dried with magnesium sulfate andconcentrated in vacuo to give the crudedl-11α,15-bistrimethylsiloxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis-13-trans-prostadienoicacid trimethylsilyl ester.

The crude trimethylsilyl ester is dissolved in 5 ml. of methanolcontaining 0.5 ml. of water and 0.25 ml. of acetic acid and stirred atambient temperature for 1 hour. The solution is diluted with 5 ml. of30% aqueous potassium hydrogen phosphate and extracted twice with 10 ml.of ether. The ether is dried with magnesium sulfate and concentrated invacuo to afforddl-11α,15α-dihydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis-13-trans-prostatrienoicacid as an oil.

The crude oil is purified by dry column chromatography on silica gel togivedl-11α,15α-dihydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis-13-trans-prostatrienoicacid.

EXAMPLES 2-57

Treatment of the compounds of the following table by the procedure ofExample 1 is productive of the 9-oxo derivatives of the table.

    __________________________________________________________________________    Ex-                                                                           ample                                                                             Starting Compound   9-Oxo Product                                         __________________________________________________________________________    2   dl-9α,11α,15α-trihydroxy-16-benzyloxy-                                          dl-11α,15α-dihydroxy-9-oxo-16-benzylox                            y-17,20-                                                  17,20-tetranor-5-cis,13-trans-prosta-                                                             tetranor-5-cis,13-trans-prostadienoic acid                dienoic acid                                                              3   dl-9α,11α,15α-trihydroxy-16-(2-naph-                                            dl-11α,15α-dihydroxy-9-oxo-16-(2-napht                            hyloxy)-                                                  yloxy)-17,20-tetranor-5-cis,13-                                                                   17,20-tetranor-5-cis,13-trans-prostadienoic               trans-prostadienoic acid                                                                          acid                                                  4   dl-9α,11α,15α-trihydroxy-16-p-chloro-                                           dl-11α,15α-dihydroxy-9-oxo-16-p-chloro                            phenoxy-                                                  phenoxy-17,20-tetranor-5-cis,13-                                                                  17,20-tetranor-5-cis,13-trans-prostadienoic               trans-prostadienoic acid                                                                          acid                                                  5   dl-9α,11α,15α-trihydroxy-16-m-chloro-                                           dl-11α,15α-dihydroxy-9-oxo-16-m-chloro                            phenoxy-                                                  phenoxy-17,20-tetranor-5-cis,13-                                                                  17,20-tetranor-5-cis,13-trans-prostadienoic               trans-prostadienoic acid                                                                          acid                                                  6   dl-9α,11α,15α-trihydroxy-16-o-chloro-                                           dl-11α,15α-dihydroxy-9-oxo-16-o-chloro                            phenoxy-                                                  phenoxy-17,20-tetranor-5-cis,13-                                                                  17,20-tetranor-5-cis,13-trans-prostadienoic               trans-prostadienoic acid                                                                          acid                                                  7   dl-9α,11α,15α-trihydroxy-16-(2,4-                                               dl-11α,15α-dihydroxy-9-oxo-16-(2,4-dic                            hloro-                                                    dichlorophenoxy)-17,20-tetranor-                                                                  phenoxy)-17,20-tetranor-5-cis,13-trans-prosta-            5-cis,13-trans-prostadienoic                                                                      dienoic acid                                              acid                                                                      8   dl-9α,11α,15α-trihydroxy-16-p-bromo-                                            dl-11α,15α-dihydroxy-9-oxo-16-p-bromop                            henoxy-                                                   phenoxy-17,20-tetranor-5-cis,13-                                                                  17,20-tetranor-5-cis,13-trans-prostadienoic               trans-prostadienoic acid                                                                          acid                                                  9   dl-9α,11α,15α-trihydroxy-16-p-fluoro-                                           dl-11α,15α-dihydroxy-9-oxo-16-p-fluoro                            phenoxy-                                                  phenoxy-17,20-tetranor-5-cis,13-                                                                  17,20-tetranor-5-cis,13-trans-prostadienoic               trans-prostadienoic acid                                                                          acid                                                  10  dl-9α,11α,15α/β-trihydroxy-16-p-                                           dl-11α,15α/β-dihydroxy-9-oxo-16-p                            -methylphenoxy-                                           methylphenoxy-17,20-tetranor-5-                                                                   17,20-tetranor-5-cis,13-trans-prostadienoic               cis,13-trans-prostadienoic acid                                                                   acid                                                  11  dl-9α,11α,15α-trihydroxy-16-m-                                                  dl-11α,15α-dihydroxy-9-oxo-16-m-methyl                            phenoxy-                                                  methylphenoxy-17,20-tetranor-5-                                                                   17,20-tetranor-5-cis,13-trans-prostadienoic               cis,13-trans-prostadienoic acid                                                                   acid                                                  12  dl-9α,11α,15α/β-trihydroxy-16-p-t-                                         dl-11α,15α/β-dihydroxy-9-oxo-16-p                            -t-butyl-                                                 butylphenoxy-17,20-tetranor-5-                                                                    phenoxy-17,20-tetranor-5-cis,13-trans-prosta-             cis,13-trans-prostadienoic acid                                                                   dienoic acid                                          13  dl-9α,11α,15α-trihydroxy-16-p-tri-                                              dl-11α,15α-dihydroxy-9-oxo-16-p-triflu                            oromethyl-                                                fluoromethylphenoxy-17,20-tetranor-                                                               phenoxy-17,20-tetranor-5-cis,13-trans-prosta-             5-cis,13-trans-prostadienoic                                                                      dienoic acid                                              acid                                                                      14  dl-9α,11α,15α-trihydroxy-16-p-                                                  dl-11α,15α-dihydroxy-9-oxo-16-p-methox                            yphenoxy-                                                 methoxyphenoxy-17,20-tetranor-                                                                    17,20-tetranor-5-cis,13-trans-prostadienoic               cis,13-trans-prostadienoic acid                                                                   acid                                                  15  dl-9α,11α,15α-trihydroxy-16-o-                                                  dl-11α,15α-dihydroxy-9-oxo-16-o-methox                            yphenoxy-                                                 methoxy-17,20-tetranor-5-cis,13-                                                                  17,20-tetranor-5-cis,13-trans-prostadienoic               trans-prostadienoic acid                                                                          acid                                                  16  dl-9α,11α,15α-trihydroxy-16-m-fluoro-                                           dl-11α,15α-dihydroxy-9-oxo-16-m-fluoro                            phenoxy-                                                  phenoxy-17,20-tetranor-5-cis,13-trans-                                                            17,20-tetranor-5-cis,13-trans-prostadienoic               prostadienoic acid  acid                                                  17  dl-9α,11α,15α-trihydroxy-16-o-fluoro-                                           dl-11α,15α-dihydroxy-9-oxo-16-o-fluoro                            phenoxy-                                                  phenoxy-17,20-tetranor-5-cis,13-trans-                                                            17,20-tetranor-5-cis,13-trans-prostadienoic               prostadienoic acid  acid                                                  18  dl-9α,11α,15α-trihydroxy-16-(3,4-                                               dl-11α,15α-dihydroxy-9-oxo-16-(3,4-dic                            hloro-                                                    dichlorophenoxy)-17,20-tetranor-                                                                  phenoxy)-17,20-tetranor-5-cis,13-trans-prosta-            5-cis,13-trans-prostadienoic acid                                                                 dienoic acid                                          19  dl-9α,11α,15α-trihydroxy-16-(2,5-                                               dl-11α,15α-dihydroxy-9-oxo-16-(2,5-dic                            hloro-                                                    dichlorophenoxy)-17,20-tetranor-5-                                                                phenoxy)-17,20-tetranor-5-cis,13-trans-prosta-            cis,13-trans-prostadienoic acid                                                                   dienoic acid                                          20  dl-9α,11α,15α-trihydroxy-16-o-methyl-                                           dl-11α,15α-dihydroxy-9-oxo-16-o-methyl                            phenoxy-                                                  phenoxy-17,20-tetranor-5-cis,13-trans-                                                            17,20-tetranor-5-cis,13-trans-prostadienoic acid          prostadienoic acid                                                        21  dl-9α,11α,15α-trihydroxy-                                                       dl-11α,15α-dihydroxy-9-oxo-16(2,3-dime                            thyl-                                                     16-(2,3-dimethylphenoxy)-17,20-                                                                   phenoxy)-17,20-tetranor-5-cis,13-trans-prosta-            tetranor-5-cis,13-trans-prosta-                                                                   dienoic acid                                              dienoic acid                                                              22  dl-9α,11α,15α-trihydroxy-16-(3,5-                                               dl-11α,15α-dihydroxy-9-oxo-16-(3,5-dim                            ethyl-                                                    dimethylphenoxy)-17,20-tetranor-                                                                  phenoxy)-17,20-tetranor-5-cis,13-trans-prosta-            5-cis,13-trans-prostadienoic acid                                                                 dienoic acid                                          23  dl-9α,11α,15α-trihydroxy-16-(2-chloro-                                          dl-11α,15α-dihydroxy-9-oxo-16-(2-chlor                            o-4-                                                      4-methylphenoxy)-17,20-tetranor-5-                                                                methylphenoxy)-17,20-tetranor-5-cis,13-trans-             cis,13-trans-prostadienoic acid                                                                   prostadienoic acid                                    24  dl-9α,11α,15α-trihydroxy-16-m-dimethyl-                                         dl-11α,15α-dihydroxy-9-oxo-16-M-dimeth                            ylamino-                                                  aminophenoxy-17,20-tetranor-5-cis,                                                                phenoxy-17,20-tetranor-5-cis,13-trans-prosta-             13-trans-prostadienoic acid                                                                       dienoic acid                                          25  dl-9α,11α,15α-trihydroxy-16-(1-                                                 dl-11α,15α-dihydroxy-9-oxo-16-(1-napht                            hyloxy)-                                                  naphthyloxy)-17,20-tetranor-5-                                                                    17,20-tetranor-5-cis,13-trans-prostadienoic               cis,13-trans-prostadienoic acid                                                                   acid                                                  26  dl-9α,11α,15α-trihydroxy-16-(4-chloro-                                          dl-11α,15α-dihydroxy-9-oxo-16-(4-chlor                            o-1-                                                      1-naphthyloxy)-17,20-tetranor-5-                                                                  naphthyloxy)-17,20-tetranor-5-cis,13-trans-               cis,13-trans-prostadienoic acid                                                                   prostadienoic acid                                    27  dl-9α,11α,15α-trihydroxy-16-(6-                                                 dl-11α,15α-dihydroxy-9-oxo-16-(6-methy                            l-2-                                                      methyl-2-naphthyloxy)-17,20-tetranor-                                                             naphthyloxy)-17,20-tetranor-5-cis,13-trans-               5-cis,13-trans-prostadienoic acid                                                                 prostadienoic acid                                    28  dl-9α,11α,15α-trihydroxy-16-(6-                                                 dl-11α,15α-dihydroxy-9-oxo-16-(6-metho                            xy-2-                                                     methoxy-2-naphthyloxy)-17,20-tetra-                                                               napthyloxy)-17,20-tetranor-5-cis,13-trans-                nor-5-cis,13-trans-prostadienoic                                                                  prostadienoic acid                                        acid                                                                      29  dl-9α,11α,15-trihydroxy-16-(2,3-di-                                                   dl-11α,15α-dihydroxy-9-oxo-16-(2,3-dic                            hloro-                                                    chloro)-17,20-tetranor-5-cis-13-                                                                  phenoxy)-17,20-tetranor-5-cis,13-trans-prosta-            trans-prostadienoic acid                                                                          dienoic acid                                          30  dl-9α,11α,15α-trihydroxy-16-(2,6-di-                                            dl-11α,15α-dihydroxy-9-oxo-16-(2,6-dic                            hloro-                                                    chlorophenoxy)-17,20-tetranor-5-cis,                                                              phenoxy)-17,20-tetranor-5-cis,13-trans-prosta-            13-trans-prostadienoic acid                                                                       dienoic acid                                          31  dl-9α,11α,15α-trihydroxy-16-(3,5-                                               dl-11α,15α-dihydroxy-9-oxo-16-(3,5-dic                            hloro-                                                    dichlorophenoxy)-17,20-tetranor-                                                                  phenoxy)-17,20-tetranor-5-cis,13-trans-prosta-            5-cis,13-trans-prostadienoic acid                                                                 dienoic acid                                          32  dl-9α,11α,15α-trihydroxy-16-(4-chloro-                                          dl-11α,15α-dihydroxy-9-oxo-16-(4-chlor                            o-3-methyl-                                               3-methylphenoxy)-17,20-tetranor-5-                                                                phenoxy)-17,20-tetranor-5-cis,13-trans-prosta-            cis,13-trans-prostadienoic acid                                                                   dienoic acid                                          33  dl-9α,11α,15α-trihydroxy-16-m-methoxy-                                          dl-11α,15α-dihydroxy-9-oxo-16-m-methox                            yphenoxy-17,                                              phenoxy-17,20-tetranor-5-cis,13-                                                                  20-tetranor-5-cis,13-trans-prostadienoic acid             trans-prostadienoic acid                                                  34  dl-9α,11α,15α/β-trihydroxy-16-(1-                                          dl-11α,15α/β-dihydroxy-9-oxo-16-(                            1-chloro-2-                                               chloro-2-naphthyloxy)-17,20-tetra-                                                                naphthyloxy)-17,20-tetranor-5-cis,13-trans-               nor-5-cis,13-trans-prostadienoic                                                                  prostadienoic acid                                        acid                                                                      35  dl-9α,11α,15α-trihydroxy-16-(5,6,7-                                             dl-11α,15α-dihydroxy-9-oxo-16-(5,6,7,8                            -tetra-                                                   8-tetrahydro-2-naphthyloxy)-17,20-                                                                hydro-2-naphthyloxy)-17,20-tetranor-5-cis,13-             tetranor-5-cis,13-trans-prosta-                                                                   trans-prostadienoic acid                                  dienoic acid                                                              36  dl-9α,11α,15β-trihydroxy-16-benzyloxy-                                           dl-11α,15β-dihydroxy-9-oxo-16-benzyloxy                            -17,20-                                                   17,20-tetranor-5-cis,13-trans-prosta-                                                             tetranor-5-cis,13-trans-prostadienoic acid                dienoic acid                                                              37  dl-9α,11α,15β-trihydroxy-16-(2-naph-                                             dl-11α,15β-dihydroxy-9-oxo-16-(2-naphth                            yloxy)-                                                   thyloxy)-17,20-tetranor-5-cis,13-                                                                 17,20-tetranor-5-cis,13-trans-prostadienoic               trans-prostadienoic acid                                                                          acid                                                  38  dl-9α,11α,15β-trihydroxy-16-p-chloro-                                            dl-11α,15β-dihydroxy-9-oxo-16-p-chlorop                            henoxy-                                                   phenoxy-17,20-tetranor-5-cis,13-trans-                                                            17,20-tetranor-5-cis,13-trans-prostadienoic acid          prostadienoic acid                                                        39  dl-9α,11α,15β-trihydroxy-16-m-chloro-                                            dl-11α,15β-dihydroxy-9-oxo-16-m-chlorop                            henoxy-                                                   phenoxy-17,20-tetranor-5-cis,13-                                                                  17,20-tetranor-5-cis,13-trans-prostadienoic acid          trans-prostadienoic acid                                                  40  dl-9α,11α,15β-trihydroxy-16-o-chloro-                                            dl-11α,15β-dihydroxy-9-oxo-16-o-chlorop                            henoxy-                                                   phenoxy-17,20-tetranor-5-cis,13-trans-                                                            17,20-tetranor-5-cis,13-trans-prostadienoic acid          prostadienoic acid                                                        41  dl-9α,11α,15β-trihydroxy-16-(2,4-                                                dl-11α,15β-dihydroxy-9-oxo-16-(2,4-dich                            loro-                                                     dichlorophenoxy)-17,20-tetranor-                                                                  phenoxy-17,20-tetranor-5-cis,13-trans-prosta-             5-cis,13-trans-prostadienoic acid                                                                 dienoic acid                                          42  dl-9α,11α,15β-trihydroxy-16-p-flouro-                                            dl-11α,15β-dihydroxy-9-oxo-16-p-fluorop                            henoxy-                                                   phenoxy-17,20-tetranor-5-cis,13-                                                                  17,20-tetranor-5-cis,13-trans-prostadienoic               trans-prostadienoic acid                                                                          acid                                                  43  dl-9α,11α,15β-trihydroxy-16-m-methyl-                                            dl-11α,15β-trihydroxy-9-oxo-16-m-methyl                            phenoxy-                                                  phenoxy-17,20-tetranor-5-cis,13-                                                                  17,20-tetranor-5-cis,13-trans-prostadienoic acid          trans-prostadienoic acid                                                  44  dl-9α,11α,15β-trihydroxy-16-p-tri-                                               dl-11α,15β-dihydroxy-9-oxo-16-p-trifluo                            romethyl-                                                 fluoromethylphenoxy-17,20-tetranor-                                                               phenoxy-17,20-tetranor-5-cis,13-trans-prosta-             5-cis,13-trans-prostadienoic acid                                                                 dienoic acid                                          45  dl-9α,11α,15β-trihydroxy-16-p-methoxy-                                           dl-11α,15β-dihydroxy-9-oxo-16-p-methoxy                            phenoxy-                                                  phenoxy-17,20-tetranor-5-cis,13-                                                                  17,20-tetranor-5-cis,13-trans-prostadienoic acid          trans-prostadienoic acid                                                  46  dl-9α,11α,15β-trihydroxy-16-o-methoxy-                                           dl-11α,15β-dihydroxy-9-oxo-16-o-methoxy                            phenoxy-                                                  phenoxy-17,20-tetranor-5-cis,13-                                                                  17,20-tetranor-5-cis,13-trans-prostadienoic acid          trans-prostadienoic acid                                                  47  dl-9α,11α,15β-trihydroxy-16-m-fluoro-                                            dl-11α,15β-dihydroxy-9-oxo-16-m-fluorop                            henoxy-                                                   phenoxy-17,20-tetranor-5-cis,13-                                                                  17,20-tetranor-5-cis,13-trans-prostadienoic acid          trans-prostadienoic acid                                                  48  dl-9α,11α,15β-trihydroxy-16-o-fluoro-                                            dl-11α,15β-dihydroxy-9-oxo-16-o-fluorop                            henoxy-                                                   phenoxy-17,20-tetranor-5-cis,13-                                                                  17,20-tetranor-5-cis,13-trans-prostadienoic acid          trans-prostadienoic acid                                                  49  dl-9α,11α,15β-trihydroxy-16-o-methyl-                                            dl-11α,15β-dihydroxy-9-oxo-16-o-methylp                            henoxy-                                                   phenoxy-17,20-tetranor-5-cis,13-                                                                  17,20-tetranor-5-cis,13-trans-prostadienoic acid          trans-prostadienoic acid                                                  50  dl-9α,11α,15β-trihydroxy-16-m-dimethyl-                                          dl-11α,15β-dihydroxy-9-oxo-16-m-dimethy                            lamino-                                                   aminophenoxy-17,20-tetranor-5-cis,13-                                                             phenoxy-17,20-tetranor-5-cis,13-trans-prosta-             trans-prostadienoic acid                                                                          dienoic acid                                          51  dl-9α,11α,15β-trihydroxy-16-(1-naphth-                                           dl-11α,15β-dihydroxy-9-oxo-16-(1-naphth                            yloxy)-                                                   yloxy)-17,20-tetranor-5-cis,13-trans-                                                             17,20-tetranor-5-cis,13-trans-prostadienoic               prostadienoic acid  acid                                                  52  dl-9α,11α,15β-trihydroxy-16-(6-                                                  dl-11α,15β-dihydroxy-9-oxo-16-(6-methox                            y-2-                                                      methoxy-2-naphthyloxy)-17,20-tetra-                                                               naphthyloxy)-17,20-tetranor-5-cis,13-trans-               nor-5-cis,13-trans-prostadienoic                                                                  prostadienoic acid                                        acid                                                                      53  dl-9α,11α,15β-trihydroxy-16-(2,3-di-                                             dl-11α,15β-dihydroxy-9-oxo-16-(2,3-dich                            loro-                                                     chlorophenoxy)-17,20-tetranor-5-cis,                                                              phenoxy-17,20-tetranor-5-cis,13-trans-prosta-             13-trans-prostadienoic acid                                               54  dl-9α,11α,15β-trihydroxy-16-(3,5-                                                dl-11α,15β-dihydroxy-9-oxo-16-(3,5-dich                            loro-                                                     dichlorophenoxy)-17,20-tetranor-5-                                                                phenoxy)-17,20-tetranor-5-cis,13-trans-prosta-            cis,13-trans-prostadienoic acid                                                                   dienoic acid                                          55  dl-9α,11α,15β-trihydroxy-16-m-methoxy-                                           dl-11α,15β-dihydroxy-9-oxo-16-m-methoxy                            phenoxy-                                                  phenoxy-17,20-tetranor-5-cis,13-                                                                  17,20-tetranor-5-cis,13-trans-prostadienoic acid          trans-prostadienoic acid                                                  56  dl-9α,11α,15β-trihydroxy-16-(5,6,7,8-                                            dl-11α,15β-dihydroxy-9-oxo-16-(5,6,7,8-                            tetra-                                                    tetrahydro-2-naphthyloxy)-17,20-                                                                  hydro-2-naphthyloxy)-17,20-tetranor-5-cis,                tetranor-5-cis,13-trans-prostadienoic                                                             13-trans-prostadienoic acid                               acid                                                                      57  dl-9α,11α,15β-trihydroxy-16-phenoxy-                                             dl-11α,15β-dihydroxy-9-oxo-16-phenoxy-         17,20-tetranor-5-cis,13-trans-                                                                    17,20-tetranor-5-cis,13-trans-prostadienoic               prostadienoic acid  acid                                                  __________________________________________________________________________

EXAMPLE 58 Preparation ofdl-11α,15α-dihydroxy-9-oxo-16-phenoxy-17,20-tetranor-13-trans-prostenoicacid by hydrogenation ofdl-11α,15α-dihydro-9-oxo-16-phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid (Example 1)

A solution of 110 mg. ofdl-11α,15α-dihydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid (Example 1) in 0.5 ml. acetone and 0.5 ml. benzene is purged withargon and 11 mg. of tris(triphenylphosphine)rhodium chloride is added.This mixture is stirred under hydrogen at 20-30 psi for 6 hours, oruntil a TLC (using silver nitrate impregnated silica plate) indicatesthe absence of any prostadienoic acid. The solvents are removed in vacuoand the oily residue is dissolved in 2 ml. methanol and poured into 10ml. of 0.2 M sodium phosphate buffer. The mixture is extracted twicewith toluene. The aqueous layers are acidified to pH 3 with 2 M citricacid, saturated with sodium chloride, and extracted twice with ether.The extracts are dried with magnesium sulfate and concentrated in vacuoto give 100 mg. of an oil.

This oil is chromatographed on acid washed silica gel to give 40 mg. ofdl-11α,15α-dihydroxy-9-oxo-16-phenoxy-17,20-tetranor-13-trans-prostenoicacid; λmax. 3400, 1740-1710, 975 cm⁻¹.

EXAMPLES 59-65

Treatment of the E₂ compounds of the following table by the method ofExample 58 is productive of the E₁ compound of the table.

                  TABLE 2                                                         ______________________________________                                        Ex-   E.sub.2                                                                 ample Compound  E.sub.1 Compound                                              ______________________________________                                        59    Example 10                                                                              dl-11α,15α/β-dihydroxy-9-oxo-16-p-methyl-                    phenoxy-17,20-tetranor-13-trans-prostenoic                                    acid                                                          60    Example 11                                                                              dl-11α,15α-dihydroxy-9-oxo-16-m-methyl-                           phenoxy-17,20-tetranor-13-trans-prostenoic                                    acid                                                          62    Example 22                                                                              dl-11α,15α-dihydroxy-9-oxo-16-(3,5-di-                            methylphenoxy)-17,20-tetranor-13-trans-                                       prostenoic acid                                               62    Example 46                                                                              dl-11α,15α-dihydroxy-9-oxo-16-o-methoxy-                          phenoxy-17,20-tetranor-13-trans-prostenoic                                    acid                                                          63    Example 20                                                                              dl-11α,15β-dihydroxy-9-oxo-16-o-methyl-                            phenoxy-17,20-tetranor-13-trans-prostenoic                                    acid                                                          64    Example 45                                                                              dl-11α,15β-dihydroxy-9-oxo-16-p-methoxy-                           phenoxy-17,20-tetranor-13-trans-prostenoic                                    acid                                                          65    Example 50                                                                              dl-11α,15β-dihydroxy-9-oxo-16-m-dimethyl-                          aminophenoxy-17,20-tetranor-13-trans-                                         prostenoic acid                                               ______________________________________                                    

EXAMPLE 66 Preparation ofdl-15α-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis-10,13-trans-prostatrienoicacid

A solution of 80 mg. ofdl-11α,15α-dihydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis-13-trans-prostadienoicacid (Example 1) in 5 ml. of 0.5 N hydrochloric acid in 1:1water-tetrahydrofuran for 60 hours at 25° C.

The solution is diluted with 100 ml. of benzene and 50 ml. of brine isadded. The organic solution is concentrated in vacuo to afford the oilyproduct; λmax: 3400, 1710, 975 cm⁻¹, λmax: 217 nm (ε=9000).

EXAMPLES 67-129

The prostaglandin E compound of the table, when submitted to thereaction conditions of Example 66 gives the prostaglandin A product ofthe table.

                                      TABLE 3                                     __________________________________________________________________________    Example                                                                            Starting E Compound                                                                      Product A Compound                                            __________________________________________________________________________    67   Example 2  dl-15α-hydroxy-9-oxo-16-benzyloxy-17,20-tetranor-                       5-cis,10,13-trans-prostatrienoic acid                         68   Example 3  dl-15α-hydroxy-9-oxo-16-(2-naphthyloxy)-17,20-                          tetranor-5-cis,10,13-trans-prostatrienoic acid                69   Example 4  dl-15α-hydroxy-9-oxo-16-p-chlorophenoxy-17,20-                          tetranor-5-cis,10,13-trans-prostatrienoic acid                70   Example 5  dl-15α-hydroxy-9-oxo-16-o-chlorophenoxy-17,20-                          tetranor-5-cis,10,13-trans-prostatrienoic acid                71   Example 6  dl-15α-hydroxy-9-oxo-16-o-chlorophenoxy-17,20-                          tetranor-5-cis,10,13-trans-prostatrienoic acid                72   Example 7  dl-15α-hydroxy-9-oxo-16-(2,4-dichlorophenoxy)-                          17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid          73   Example 8  dl-15α-hydroxy-9-oxo-16-p-bromophenoxy-17,20-                           tetranor-5-cis,10,13-trans-prostatrienoic acid                74   Example 9  dl-15α-hydroxy-9-oxo-16-p-fluorophenoxy-17,20-                          tetranor-5-cis,10,13-trans-prostatrienoic acid                75   Example 10 dl-15α/β-hydroxy-9-oxo-16-p-methylphenoxy-17,20                    -                                                                             tetranor-5-cis,10,13-trans-prostatrienoic acid                76   Example 11 dl-15α-hydroxy-9-oxo-16-m-methylphenoxy-17,20-                          tetranor-5-cis,10,13-trans-prostatrienoic acid                77   Example 12 dl-15α/β-hydroxy-9-oxo-16-p-t-butylphenoxy-17,2                    0-                                                                            tetranor-5-cis,10,13-trans-prostatrienoic acid                78   Example 13 dl-15α-hydroxy-9-oxo-16-p-trifluoromethylphenoxy-                       17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid          79   Example 14 dl-15α-hydroxy-9-oxo-16-p-methoxyphenoxy-17,20-                         tetranor-5-cis,10,13-trans-prostatrienoic acid                80   Example 15 dl-15α-hydroxy-9-oxo-16-o-methoxyphenoxy-17,20-                         tetranor-5-cis,10,13-trans-prostatrienoic acid                81   Example 16 dl-15α-hydroxy-9-oxo-16-m-fluorophenoxy-17,20-                          tetranor-5-cis,10,13-trans-prostatrienoic acid                82   Example 17 dl-15α-hydroxy-9-oxo-16-o-fluorophenoxy-17,20-                          tetranor-5-cis,10,13-trans-prostatrienoic acid                83   Example 18 dl-15α-hydroxy-9-oxo-16-(3,4-dichlorophenoxy)-                          17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid          84   Example 19 dl-15α-hydroxy-9-oxo-16-(2,5-dichlorophenoxy)-                          17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid          85   Example 20 dl-15α-hydroxy-9-oxo-16-o-methylphenoxy-17,20-                          tetranor-5-cis,10,13-trans-prostatrienoic acid                86   Example 21 dl-15α-hydroxy-9-oxo-16-(2,3-dimethylphenoxy)-                          17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid          87   Example 22 dl-15α-hydroxy-9-oxo-16-(3,5-dimethylphenoxy)-                          17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid          88   Example 23 dl-15α-hydroxy-9-oxo-16-(2-chloro-4-methylphenoxy)-                     17,20-tetranor-5-cis,10,13-trans-prostatrienoic                               acid                                                          89   Example 24 dl-15α-hydroxy-9-oxo-16-m-dimethylaminophenoxy-                         17,20-tetranor-5-cis,10,13-trans-prostatrienoic                               acid                                                          90   Example 25 dl-15α-hydroxy-9-oxo-16-(1-naphthyloxy)-17,20-                          tetranor-5-cis,10,13-trans-prostatrienoic acid                91   Example 26 dl-15α-hydroxy-9-oxo-16-(4-chloro-1-naphthyloxy)-                       17,20-tetranor-5-cis,10,13-trans-prostatrienoic                               acid                                                          92   Example 27 dl-15α-hydroxy-9-oxo-16-(6-methyl-2-naphthyloxy)-                       17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid          93   Example 28 dl-15α-hydroxy-9-oxo-16-(6-methoxy-2-naphthyloxy-                       17,20-tetranor-5-cis,10,13-trans-prostatrienoic                               acid                                                          94   Example 29 dl-15α-hydroxy-9-oxo-16-(2,3-dichlorophenoxy)-                          17,20-tetranor-5-cis,10,13-trans-prostatrienoic                               acid                                                          95   Example 30 dl-15α-hydroxy-9-oxo-16-(2,6-dichlorophenoxy)-17,                       20-tetranor-5-cis,10,13-trans-prostatrienoic acid             96   Example 31 dl-15α-hydroxy-9-oxo-16-(3,5-dichlorophenoxy)-                          17,20-tetranor-5-cis,10,13-trans-prostatrienoic                               acid                                                          97   Example 32 dl-15α-hydroxy-9-oxo-16-(4-chloro-3-methylphenoxy)-                     17,20-tetranor-5-cis,10,13-trans-prostatrienoic                               acid                                                          98   Example 33 dl-15α-hydroxy-9-oxo-16-m-methoxyphenoxy-17,20-                         tetranor-5-cis,10,13-trans-prostatrienoic acid                99   Example 34 dl-15α/β-hydroxy-9-oxo-16-(1-chloro-2-naphthylo                    xy)-                                                                          17,20-tetranor-5-cis,10,13-trans-prostatrienoic                               acid                                                          100  Example 35 dl-15α-hydroxy-9-oxo-16-(5,6,7,8-tetrahydro-2-                          naphthyloxy)-17,20-tetranor-5-cis,10,13-trans-                                prostatrienoic acid                                           101  Example 36 dl-15β-hydroxy-9-oxo-16-benzyloxy-17,20-tetranor-                        5-cis,10,13-trans-prostatrienoic acid                         102  Example 37 dl-15β-hydroxy-9-oxo-16-(2-naphthyloxy)-17,20-                           tetranor-5-cis,10,13-trans-prostatrienoic acid                103  Example 38 dl-15α-hydroxy-9-oxo-16-p-chlorophenoxy-17,20-                          tetranor-5-cis,10,13-trans-prostatrienoic acid                104  Example 39 dl-15β-hydroxy-9-oxo-16-m-chlorophenoxy-17,20-                           tetranor-5-cis,10,13-trans-prostatrienoic acid                105  Example 40 dl-15β-hydroxy-9-oxo-16-o-chlorophenoxy-17,20-                           tetranor-5-cis,10,13-trans-prostatrienoic acid                106  Example 41 dl-15β-hydroxy-9-oxo-16-(2,4-dichlorophenoxy)-                           17,20-tetranor-5-cis,10,13-trans-prostatrienoic                               acid                                                          107  Example 42 dl-15β-hydroxy-9-oxo-16-p-fluorophenoxy-17,20-                           tetranor-5-cis,10,13-trans-prostatrienoic acid                108  Example 43 dl-15β-hydroxy-9-oxo-16-m-methylphenoxy-17,20-                           tetranor-5-cis,10,13-trans-prostatrienoic acid                109  Example 44 dl-15β-hydroxy-9-oxo-16-p-trifluoromethylphenoxy-                        17,20-tetranor-5-cis,10,13-trans-prostatrienoic                               acid                                                          110  Example 45 dl-15β-hydroxy-9-oxo-16-p-methoxyphenoxy-17,20-                          tetranor-5-cis,10,13-trans-prostatrienoic acid                111  Example 46 dl-15β-hydroxy-9-oxo-16-o-methoxyphenoxy-17,20-                          tetranor-5-cis,10,13-trans-prostatrienoic acid                112  Example 47 dl-15β-hydroxy-9-oxo-16-m-fluorophenoxy-17,20-                           tetranor-5-cis,10,13-trans-prostatrienoic acid                113  Example 48 dl-15β-hydroxy-9-oxo-16-o-fluorophenoxy-17,20-                           tetranor-5-cis,10,13-trans-prostatrienoic acid                114  Example 49 dl-15β-hydroxy-9-oxo-16-o-methylphenoxy-17,20-                           tetranor-5-cis,10,13-trans-prostatrienoic acid                115  Example 50 dl-15β-hydroxy-9-oxo-16-m-dimethylaminophenoxy-                          17,20-tetranor-5-cis,10,13-trans-prostatrienoic                               acid                                                          116  Example 51 dl-15β-hydroxy-9-oxo-16-(1-naphthyloxy)-17,20-tetra-                     nor-5-cis,10,13-trans-prostatrienoic acid                     117  Example 52 dl-15β-hydroxy-9-oxo-16-(6-methoxy-2-naphthyloxy)-17,                    20-tetranor-5-cis,10,13-trans-prostatrienoic acid             118  Example 53 dl-15β-hydroxy-9-oxo-16-(2,3-dichlorophenoxy)-17,                        20-tetranor-5-cis,10,13-trans-prostatrienoic acid             119  Example 54 dl-15β-hydroxy-9-oxo-16-(3,5-dichlorophenoxy)-17,                        20-tetranor-5-cis,10,13-trans-prostatrienoic acid             120  Example 55 dl-15β-hydroxy-9-oxo-16-m-methoxyphenoxy-17,20-                          tetranor-5-cis,10,13-trans-prostatrienoic acid                121  Example 56 dl-15β-hydroxy-9-oxo-16-(5,6,7,8-tetrahydro-2-                           naphthyloxy)-17,20-tetranor-5-cis,10,13-trans-                                prostatrienoic acid                                           122  Example 57 dl-15β-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-                          5-cis,10,13-trans-prostatrienoic acid                         123  Example 58 dl-15α-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-                         10,13-trans-prostadienoic acid                                124  Example 60 dl-15α-hydroxy-9-oxo-16-m-methylphenoxy-17,20-                          tetranor-10,13-trans-prostadienoic acid                       125  Example 61 dl-15α-hydroxy-9-oxo-16-(3,5-dimethylphenoxy)-                          17,20-tetranor-10,13-trans-prostadienoic acid                 126  Example 62 dl-15β-hydroxy-9-oxo-16-o-methoxyphenoxy-17,20-                          tetranor-10,13-trans-prostadienoic acid                       127  Example 63 dl-15α-hydroxy-9-oxo-16-o-methylphenoxy-17,20-                          tetranor-10,13-trans-prostadienoic acid                       128  Example 64 dl-15β-hydroxy-9-oxo-16-p-methoxyphenoxy-17,20-                          tetranor-10,13-trans-prostadienoic acid                       129  Example 65 dl-15β-hydroxy-9-oxo-16-m-dimethylaminophenoxy-                          17,20-tetranor-10,13-trans-prostadienoic acid                 129a Example 59 dl-11α,15α  /β-dihydroxy-9-oxo-16-p-methy                    lphenoxy-                                                                     17,20-tetranor-10,13-trans-prostadienoic                      __________________________________________________________________________                    acid                                                      

EXAMPLE 130 Preparation ofdl-11-deoxy-15α-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid

150 mg. ofdl-15α-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,10,13-trans-prostatrienoicacid (Example 66) in 10 ml. of ether is esterified with excessdiazomethane in ether. Evaporation of the ether givesdl-15α-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,10,13-trans-prostatrienoicacid methyl ester.

The crude methyl ester is dissolved in 10 ml. of benzene and 7 ml. of a1 N solution of acetic anhydride-pyridine in benzene is added. After 24hours 5 ml. more of 1 N acetic anhydride-piperidine is added andstirred. After an additional 24 hours, 5 ml. more of 1 N aceticanhydride-pyridine is added and stirred 72 hours or until TLC indicatesno starting material present. The volume of the reaction is reduced to10 ml. in vacuo on a rotary evaporator. The reaction product ischromatographed on acid washed silica-gel with ethyl acetate-benzene toprovidedl-15α-acetoxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,10,13-trans-prostatrienoicacid methyl ester as an oil.

The crude methyl ester is dissolved in 3 ml. of ethanol at 0° C. and istreated dropwise with a cold solution of 230 mg. of sodium borohydridein 3 ml. of ethanol containing 0.3 ml. of water. After 15 minutes, 0.25ml. of acetic acid and 10 ml. of water is added, and the mixture isextracted with 50 ml. of methylene chloride. The organic extract iswashed with sodium bicarbonate, dried with magnesium sulfate, andconcentrated in vacuo to give an oil.

The crude oil is dissolved in 8 ml. of acetone and cooled to -5° C. Then0.3 ml. of Jones chromic oxide mixture is added slowly and after 15minutes 0.1 ml. of isopropanol is added.

After 5 minutes the solution is diluted with 25 ml. of methylenechloride and washed with 20 ml. of water. The methylene chloride isdried with magnesium sulfate and concentrated in vacuo to give the crudemixture as an oil.

The oil is purified on acid washed silica-gel using benzene-ethylacetate to givedl-15α-acetoxy-11-deoxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid methyl ester as an oil.

To 50 mg. of the methyl ester in 2 ml. of methanol is added 1 ml. of 2.5N aqueous sodium hydroxide. After stirring for 8 hours, the solution isacidified with 30% aqueous sodium dihydrogen phosphate, saturated withsodium chloride, and extracted with ether. The ether extracts are driedwith magnesium sulfate and concentrated in vacuo to givedl-11-deoxy-15α-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid; 3400, 1735, 1710, 975 cm⁻¹.

EXAMPLES 131-194

Treatment of the A type compounds of the table by the method of Example130 is productive of the 11-deoxy compounds of the table.

                                      TABLE 4                                     __________________________________________________________________________         Starting                                                                 Example                                                                            Prostaglandin A                                                                       11-Deoxy Product                                                 __________________________________________________________________________    131  Example 67                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-benzyloxy-17,20-                       tetranor-5-cis,13-trans-prostadienoic acid                       132  Example 68                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-(2-naphthyloxy)-                       17,20-tetranor-5-cis,13-trans-prostadienoic acid                 133  Example 69                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-p-chlorophenoxy-                       17,20-tetranor-5-cis,13-trans-prostadienoic acid                 134  Example 70                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-m-chlorophenoxy-                       17,20-tetranor-5-cis,13-trans-prostadienoic acid                 135  Example 71                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-o-chlorophenoxy-                       17,20-tetranor-5-cis,13-trans-prostadienoic acid                 136  Example 72                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-(2,4-dichlorophenoxy)-                 17,20-tetranor-5-cis,13-trans-prostadienoic acid                 137  Example 73                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-p-bromophenoxy-                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                 138  Example 74                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-p-fluorophenoxy-                       17,20-tetranor-5-cis,13-trans-prostadienoic acid                 139  Example 75                                                                            dl-11-deoxy-15α/β-hydroxy-9-oxo-16-p-methylphenoxy                 -                                                                             17,20-tetranor-5-cis,13-trans-prostadienoic acid                 140  Example 76                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-m-methylphenoxy-                       17,20-tetranor-5-cis,13-trans-prostadienoic acid                 141  Example 77                                                                            dl-11-deoxy-15α/β-hydroxy-9-oxo-16-p-t-butylphenox                 y-                                                                            17,20-tetranor-5-cis,13-trans-prostadienoic acid                 142  Example 78                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-p-trifluoromethyl-                     phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoic acid         143  Example 79                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-p-methoxyphenoxy-                      17,20-tetranor-5-cis,13-trans-prostadienoic acid                 144  Example 80                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-o-methoxyphenoxy-                      17,20-tetranor-5-cis,13-trans-prostadienoic acid                 145  Example 81                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-m-fluorophenoxy-                       17,20-tetranor-5-cis,13-trans-prostadienoic acid                 146  Example 82                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-o-fluorophenoxy-                       17,20-tetranor-5-cis,13-trans-prostadienoic acid                 147  Example 83                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-(3,4-dichlorophenoxy)-                 17,20-tetranor-5-cis,13-trans-prostadienoic acid                 148  Example 84                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-(2,5-dichlorophenoxy)-                 17,20-tetranor-5-cis,13-trans-prostadienoic acid                 149  Example 85                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-o-methylphenoxy-                       17,20-tetranor-5-cis,13-trans-prostadienoic acid                 150  Example 86                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-(2,3-dimethyl-                         phenoxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid        151  Example 87                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-(3,5-dimethyl-                         phenoxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid        152  Example 88                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-(2-chloro-4-methyl-                    phenoxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid        153  Example 89                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-m-dimethylaminophenoxy                 -                                                                             17,20-tetranor-5-cis,13-trans-prostadienoic acid                 154  Example 90                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-(1-naphthyloxy)-                       17,20-tetranor-5-cis,13-trans-prostadienoic acid                 155  Example 91                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-(4-chloro-1-naphthylox                 y)-                                                                           17,20-tetranor-5-cis,13-trans-prostadienoic acid                 156  Example 92                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-(6-methyl-2-naphthylox                 y)-                                                                           17,20-tetranor-5-cis,13-trans-prostadienoic acid                 157  Example 93                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-(6-methoxy-2-naphth-                   yloxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid          158  Example 94                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-(2,3-dichlorophenoxy)-                 17,20-tetranor-5-cis,13-trans-prostadienoic acid                 159  Example 95                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-(2,6-dichlorophenoxy)-                 7                                                                             17,20-tetranor-5-cis,13-trans-prostadienoic acid                 160  Example 96                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-(3,5-dichlorophenoxy)-                 1                                                                             17,20-tetranor-5-cis,13-trans-prostadienoic acid                 161  Example 97                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-(4-chloro-3-methyl-                    phenoxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid        162  Example 98                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-m-methoxyphenoxy-                      17,20-tetranor-5-cis,13-trans-prostadienoic acid                 163  Example 99                                                                            dl-11-deoxy-15α/-hydroxy-9-oxo-16-(1-chloro-2-naphthyl-                 oxy)17,20-tetranor-5-cis,13-trans-prostadienoic acid             164  Example 100                                                                           dl-11-deoxy-15α-hydroxy-9-oxo-16-(5,6,7,8-tetrahydro-                   2-naphthyloxy)-17,20-tetranor-5-cis,13-trans-prosta-                          dienoic acid                                                     165  Example 101                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-benzyloxy-17,20-tetra-                  nor-5-cis,13-trans-prostadienoic acid                            166  Example 102                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-(2-naphthyloxy)-                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                 167  Example 103                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-p-chlorophenoxy-                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                 168  Example 104                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-m-chlorophenoxy-                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                 169  Example 105                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-o-chlorophenoxy-                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                 170  Example 106                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-p-fluorophenoxy-                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                 172  Example 109                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-m-methylphenoxy-                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                 173  Example 109                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-p-trifluoromethyl-                      phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoic acid         174  Example 110                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-p-methoxyphenoxy-                       17,20-tetranor-5-cis,13-trans-prostadienoic acid                 175  Example 111                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-m-methoxyphenoxy-                       17,20-tetranor-5-cis,13-trans-prostadienoic acid                 176  Example 112                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-m-fluorophenoxy-                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                 177  Example 113                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-o-fluorophenoxy-                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                 178  Example 114                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-o-methylphenoxy-                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                 179  Example 115                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-m-dimethylaminophenoxy-                 17,20-tetranor-5-cis,13-trans-prostadienoic acid                 180  Example 116                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-(1-naphthyloxy)-                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                 181  Example 117                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-(6-methoxy-2-naphthyl-                  oxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid            182  Example 118                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-(2,3-dichlorophenoxy)-                  17,20-tetranor-5-cis,13-trans-prostadienoic acid                 183  Example 119                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-(3,5-dichlorophenoxy)-                  17,20-tetranor-5-cis,13-trans-prostadienic acid                  184  Example 120                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-m-methoxyphenoxy-                       17,20-tetranor-5-cis,13-trans-prostadienoic acid                 185  Example 121                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-(5,6,7,8-tetrahydro-                    2-naphthyloxy)-17,20-tetranor-5-cis,13-trans-                                 prostadienoic acid                                               186  Example 122                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-phenoxy-17,20-                          tetranor-5-cis,13-trans-prostadienoic acid                       187  Example 123                                                                           dl-11-deoxy-15α-hydroxy-9-oxo-16-phenoxy-17,20-                         tetranor-13-trans-prostenoic acid                                188  Example 129a                                                                          dl-11-deoxy-15α/β-hydroxy-9-oxo-16-p-methylphenoxy                 -                                                                             17,20-tetranor-13-trans-prostenoic acid                          189  Example 124                                                                           dl-11-deoxy-15α-hydroxy-9-oxo-16-m-methylphenoxy-                       17,20-tetranor-13-trans-prostenoic acid                          190  Example 125                                                                           dl-11-deoxy-15α-hydroxy-9-oxo-16-(3,5-dimethylphenoxy)-                 O                                                                             17,20-tetranor-13-trans-prostenoic acid                          191  Example 126                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-o-methoxyphenoxy-                       17,20-tetranor-13-trans-prostenoic acid                          192  Example 127                                                                           dl-11-deoxy-15α-hydroxy-9-oxo-16-o-methylphenoxy-                       17,20-tetranor-13-trans-prostenoic acid                          193  Example 128                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-p-methoxyphenoxy-                       17,20-tetranor-13-trans-prostenoic acid                          194  Example 129                                                                           dl-11-deoxy-15β-hydroxy-9-oxo-16-m-dimethylamino-                        phenoxy-17,20-tetranor-13-trans-prostenoic                       __________________________________________________________________________                 acid                                                         

EXAMPLE 195 Preparation ofdl-11-deoxy-9-oxo-15α-hydroxy-16-phenoxy-17,20-tetranor-prostanoic acid

A solution of 900 mg. ofdl-11-deoxy-9-oxo-15α-hydroxy-16-phenoxy-17,20-tetranor-13-trans-prostenoicacid (Example 187) in 1 ml. of acetone and 1 ml. of benzene was purgedwith nitrogen and 0.1 gm. of tris(triphenylphosphine)rhodium chloride isadded. The mixture is shaken under 20-30 pounds of hydrogen for 12hours. The mixture is diluted with 50 ml. of 5% aqueous sodium carbonateand extracted with 10 ml. of toluene. The aqueous solution is acidifiedto pH 4 with 2 N aqueous hydrochloric acid saturated with sodiumchloride, and extracted twice with 50 ml. of ether. The ether is driedwith magnesium sulfate and concentrated in vacuo to givedl-11-deoxy-9-oxo-16-phenoxy-17,20-tetranorprostanoic acid; max. 3400,1735 cm⁻¹.

EXAMPLES 196-202

Hydrogenation of the E₁ compounds of the following table by theprocedure of Example 195 is productive of the 13-dihydro compounds ofthe table.

                  TABLE 5                                                         ______________________________________                                              Starting                                                                      13-trans-                                                               Ex-   proste-                                                                 ample noic acid                                                                              Product Prostanoic Acid                                        ______________________________________                                        196   Example  dl-11-deoxy-15α/β-hydroxy-9-oxo-16-p-methyl-              188      phenoxy-17,20-tetranor-prostanoic acid                         197   Example  dl-11-deoxy-15α-hydroxy-9-oxo-16-m-methyl-                     189      phenoxy-17,20-tetranor-prostanoic acid                         198   Example  dl-11-deoxy-15α-hydroxy-9-oxo-16-(3,5-di-                      190      methylphenoxy)-17,20-tetranor-prostanoic acid                  199   Example  dl-11-deoxy-15β-hydroxy-9-oxo-16-O--meth-                       191      oxyphenoxy-17,20-tetranor-prostanoic acid                      200   Example  dl-11-deoxy-15α-hydroxy-9-oxo-16-O--methyl-                    192      phenoxy-17,20-tetranor-prostanoic acid                         201   Example  dl-11-deoxy-15β -hydroxy-9-oxo-16-p-methoxy-                    193      phenoxy-17,20-tetranor-prostanoic acid                         202   Example  dl-11-deoxy-15β-hydroxy-9-oxo-16-m-dimethyl-                    194      aminophenoxy-17,20-tetranor-prostanoic acid                

EXAMPLE 203 Preparation ofdl-11-deoxy-9α,15α-dihydroxy-16-phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid

To 5 ml. of a -78° C. solution of 1 M lithium-tri-sec-butylborohydridein tetrahydrofuran is added slowly a cold solution of 600 mg. ofdl-11-deoxy-15α-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid in 5 ml. of tetrahydrofuran. After 20 minutes at -78° C., 2 ml. of2.5 N aqueous sodium hydroxide is added and the solution is stirred in a30° C. bath for 40 minutes. The solution is diluted with 10 ml. of waterand extracted three times with 20 ml. of ether.

The aqueous solution is acidified to pH 4 with 6 N hydrochloric acid,saturated with sodium chloride and extracted twice with 50 ml. of ether.The ether extracts are combined, dried with magnesium sulfate andconcentrated in vacuo to givedl-11-deoxy-9α,15α-dihydroxy-16-phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid; λ max. 3400, 1710, 975 cm⁻¹.

EXAMPLES 204-272

Treatment of the 9-oxo compounds of the following table by the method ofExample 203 is productive of the 9α-hydroxy compounds of the table.

                                      TABLE 6                                     __________________________________________________________________________    Example                                                                            9-Oxo Compound                                                           __________________________________________________________________________                    9α-Hydroxy Product                                      204  Example 131                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-benzyl-17,20-tet                  ranor-                                                                        5-cis,13-trans-prostadienoic acid                               205  Example 132                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-(2-naphthyloxy)-                  O                                                                             17,20-tetranor-5-cis,13-trans-prostadienoic acid                206  Example 133                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-p-chlorophenoxy-                  17,20-tetranor-5-cis,13-trans-prostadienoic acid                207  Example 134                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-m-chlorophenoxy-                  17,20-tetranor-5-cis,13-trans-prostadienoic acid                208  Example 135                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-o-chlorophenoxy-                  17,20-tetranor-5-cis,13-trans-prostadienoic acid                209  Example 136                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-(2,4-dichlorophe                  noxy)-                                                                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                210  Example 137                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-p-bromophenoxy-                   17,20-tetranor-5-cis,13-trans-prostadienoic acid                211  Example 138                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-p-fluorophenoxy-                  N                                                                             17,20-tetranor-5-cis,13-trans-prostadienoic acid                212  Example 139                                                                            dl-11-deoxy-9α,15α/β-dihydroxy-16-p-methylp                  henoxy-                                                                       17,20-tetranor-5-cis,13-trans-prostadienoic acid                213  Example 140                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-m-methylphenoxy-                  17,20-tetranor-5-cis,13-trans-prostadienoic acid                214  Example 141                                                                            dl-11-deoxy-9α,15α/β-dihydroxy-16-p-t-butyl                  phenoxy-                                                                      17,20-tetranor-5-cis,13-trans-prostadienoic acid                215  Example 142                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-p-trifluoromethy                  l-                                                                            phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoic acid        216  Example 143                                                                            dl-11-deoxy-9α,15α-dehydroxy-16-p-methoxyphenoxy                  -                                                                             17,20-tetranor-5-cis,13-trans-prostadienoic acid                217  Example 144                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-o-methoxyphenoxy                  -                                                                             17,20-tetranor-5-cis,13-trans-prostadienoic acid                218  Example 145                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-m-fluorophenoxy-                  N                                                                             17,20-tetranor-5-cis,13-trans-prostadienoic acid                219  Example 146                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-o-fluorophenoxy-                  O                                                                             17,20-tetranor-5-cis,13-trans-prostadienoic acid                220  Example 147                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-(3,4-dichlorophe                  noxy-                                                                         17,20-tetranor-5-cis,13-trans-prostadienoic acid                221  Example 148                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-(2,5-dichlorophe                  noxy)-                                                                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                222  Example 149                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-o-methylphenoxy-                  17,20-tetranor-5-cis,13-trans-prostadienoic acid                223  Example 150                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-(2,5-dimethylphe                  noxy)-                                                                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                224  Example 151                                                                            dl-11-deoxy-11α,15α-dihydroxy-16-(3,5-dimethylph                  enoxy)-                                                                       17,20-tetranor-5-cis,13-trans-prostadienoic acid                225  Example 152                                                                            dl-11-deoxy-11α,15α-dihydroxy-16-(2-chloro-4-met                  hyl-                                                                          phenoxy)-17,20-tetranor-5-cis,13-trans-prostadienoic                          acid                                                            226  Example 153                                                                            dl-11-deoxy-11α,15α-dihydroxy-16-m-dimethylamino                  -                                                                             phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoic                           acid                                                            227  Example 154                                                                            dl-11-deoxy-11α,15α-dihydroxy-16-(1-naphthyloxy)                  -17,                                                                          20-tetranor-5-cis,13-trans-prostadienoic acid                   228  Example 155                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-(4-chloro-1-naph                  thyl-                                                                         oxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid           229  Example 156                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-(6-methyl-2-naph                  thyl-                                                                         oxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid           230  Example 157                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-(6-methoxy-2-nap                  hthyl-                                                                        oxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid           231  Example 158                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-(2,3-dichlorophe                  noxy)-                                                                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                232  Example 159                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-(2,6-dichlorophe                  noxy)-                                                                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                                  9α-Compound                                           233  Example 160                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-(3,5-dichlorophe                  noxy)-                                                                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                234  Example 161                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-(4-chloro-3-meth                  yl-                                                                           phenoxy)-17,20-tetranor-5-cis,13-trans-prostadienoic                          acid                                                            235  Example 162                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-m-methoxyphenoxy                  -17,20-                                                                       tetranor-5-cis,13-trans-prostadienoic acid                      236  Example 163                                                                            dl-11-deoxy-9α,15α/β-dihydroxy-16-(1-chloro                  -2-naphthyl-                                                                  oxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid           237  Example 164                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-(5,6,7,8-tetrahy                  dro-                                                                          2-naphthyloxy)-17,20-tetranor-5-cis,13-trans-prosta-                          dienoic acid                                                    238  Example 165                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-benzyloxy-17,20-t                  etra-                                                                         nor-5-cis,13-trans-prostadienoic acid                           239  Example 166                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-(2-naphthyloxy)-1                  7,20-                                                                         tetranor-5-cis,13-trans-prostadienoic acid                      240  Example 167                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-p-chlorophenoxy-1                  7,20-                                                                         tetranor-5-cis,13-trans-prostadienoic acid                      241  Example 168                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-m-chlorophenoxy-                   17,20-tetranor-5-cis,13-trans-prostadienoic acid                242  Example 169                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-o-chlorophenoxy-                   17,20-tetranor-5-cis,13-trans-prostadienoic acid                243  Example 170                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-(2,4-dichlorophen                  oxy)-                                                                         17,20-tetranor-5-cis,13-trans-prostadienoic acid                244  Example 171                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-p-fluorophenoxy-                   B                                                                             17,20-tetranor-5-cis,13-trans-prostadienoic acid                245  Example 172                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-m-methylphenoxy-                   S                                                                             17,20-tetranor-5-cis,13-trans-prostadienoic acid                246  Example 173                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-p-trifluoromethyl                  -                                                                             phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoic                           acid                                                            247  Example 174                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-p-methoxyphenoxy-                  17,20-tetranor-5-cis,13-trans-prostadienoic acid                248  Example 175                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-o-methoxyphenoxy-                  17,20-tetranor-5-cis,13-trans-prostadienoic acid                249  Example 176                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-m-fluorophenoxy-1                  7,20-                                                                         tetranor-5-cis,13-trans-prostadienoic acid                      250  Example 177                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-o-fluorophenoxy-1                  7,20-                                                                         tetranor-5-cis,13-trans-prostadienoic acid                      251  Example 178                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-o-methylphenoxy-                   17,20-tetranor-5-cis,13-trans-prostadienoic acid                252  Example 179                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-m-dimethylamino-                   phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoic acid        253  Example 180                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-(1-naphthyloxy)-1                  7,20-                                                                         tetranor-5-cis,13-trans-prostadienoic acid                      254  Example 181                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-(6-methoxy-2-naph                  thyl-                                                                         oxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid           255  Example 182                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-(2,3-dichlorophen                  oxy)-                                                                         17,20-tetranor-5-cis,13-trans-prostadienoic acid                256  Example 183                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-(3,5-dichlorophen                  oxy)-                                                                         17,20-tetranor-5-cis,13-trans-prostadienoic acid                  257A                                                                             Example 184                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-m-methoxyphenoxy-                  17,20-tetranor-5-cis,13-trans-prostadienoic acid                  257B                                                                             Example 185                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-(5,6,7,8-tetrahyd                  ro-                                                                           2-naphthyloxy)-17,20-tetranor-5-cis,13-trans-                                 prostadienoic acid                                                257C                                                                             Example 186                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-phenoxy-17,20-                     tetranor-5-cis,13-trans-prostadienoic acid                      258  Example 187                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-phenoxy-17,20-                     tetranor-13-trans-prostenoic acid                               259  Example 189                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-m-methylphenoxy-                  17,20-tetranor-13-trans-prostenoic acid                         260  Example 190                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-(3,5-dimethylphe                  noxy)-                                                                        17,20-tetranor-13-trans-prostenoic acid                         261  Example 191                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-o-methoxyphenoxy-                  0                                                                             17,20-tetranor-13-trans-prostenoic acid                         262  Example 192                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-o-methylphenoxy-                  0                                                                             17,20-tetranor-13-trans-prostenoic acid                         263  Example 193                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-p-methoxyphenoxy-                  9                                                                             17,20-tetranor-13-trans-prostenoic acid                         264  Example 194                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-m-dimethylamino-                   phenoxy-17,20-tetranor-13-trans-prostenoic acid                 265  Example 195                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-phenoxy-17,20-                    tetranor-prostanoic acid                                        266  Example 196                                                                            dl-11-deoxy-9α,15α/β-dihydroxy-16-p-methylp                  henoxy-                                                                       17,20-tetranor-13-trans-prostenoic acid                         267  Example 197                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-m-methylphenoxy-                  17,20-tetranor-13-trans-prostenoic acid                         268  Example 198                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-(3,5-dimethylphe                  noxy)-                                                                        17,20-tetranor-13-trans-prostenoic acid                         269  Example 199                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-o-methoxyphenoxy-                  17,20-tetranor-13-trans-prostenoic acid                         270  Example 200                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-o-methylphenoxy-                  17,20-tetranor-13-trans-prostenoic acid                         271  Example 201                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-p-methoxyphenoxy-                  17,20-tetranor-13-trans-prostenoic acid                         272  Example 202                                                                            dl-11-deoxy-9α,15β-dihydroxy-16-m-dimethylaminoph                  enoxy-                                                                        17,20-tetranor-13-trans-prostenoic acid                         __________________________________________________________________________

EXAMPLE 273 Preparation ofdl-11-deoxy-9α/β,15α-dihydroxy-16-phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid and separation of the 9α and 9β components

To a 0° C. solution of 500 mg. ofdl-11-deoxy-15α-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid in 10 ml. of ethanol is added 100 mg. of sodium borohydride. After30 minutes the solution is diluted with 50 ml. of saturated aqueousammonium chloride and extracted twice with 50 ml. of ether. The ether isdried with magnesium sulfate and concentrated in vacuo to give a nearly1:1 mixture of the 9α and 9β diols.

The diol mixture is placed onto a dry column of acid washed silica anddeveloped with ethyl acetate-benzene.

The high Rf compound is isolated and isdl-11-deoxy-9α,15α-dihydroxy-16-phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid. The lower Rf, more polar isomer, isdl-11-deoxy-9β,15α-dihydroxy-16-phenoxy-17,20-tetranor-5-cis,13-trans-prostadiencicacid; the infrared spectrum of each is indentical: 3400, 1700, 975 cm⁻¹.

EXAMPLES 274-345

Treatment of the 9-oxo compounds of the following table with sodiumborohydride followed by separation by the method of Example 273 isproductive of the separated 9,15-diols of the table.

                                      TABLE 7                                     __________________________________________________________________________    Example                                                                            9-Oxo Compound                                                                            Product 9,15-Diols                                           __________________________________________________________________________    274  Example 131                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-benzyloxy                  -17,20-                                                                       tetranor-5-cis,13-trans-prostadienoic acid                      275  Example 132                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-(2-naphth                  yloxy)-17,20-                                                                 tetranor-5-cis,13-trans-prostadienoic acid                      276  Example 133                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-p-chlorop                  henoxy-17,20-                                                                 tetranor-5-cis,13-trans-prostadienoic acid                      277  Example 134                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-m-chlorop                  henoxy-17,20-                                                                 tetranor-5-cis,13-trans-prostadienoic acid                      278  Example 135                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-o-chlorop                  henoxy-17,20-                                                                 tetranor-5-cis,13-trans-prostadienoic acid                      279  Example 136                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-(2,4-dich                  lorophenoxy)-                                                                 17,20-tetranor-5-cis,13-trans-prostadienoic acid                280  Example 137                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-p-bromoph                  enoxy-17,20-                                                                  tetranor-5-cis,13-trans-prostadienoic acid                      281  Example 138                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-p-fluorop                  henoxy-17,20-                                                                 tetranor-5-cis,13-trans-prostadienoic acid                      282  Example 139                                                                            dl-11-deoxy-9α/β,15α/β-dihydroxy-16-p-                  methylphenoxy-17,20-                                                          tetranor-5-cis,13-trans-prostadienoic acid                      283  Example 140                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-m-methylphenoxy-                  17,20-                                                                        tetranor-5-cis,13-trans-prostadienoic acid                      284  Example 141                                                                            dl-11-deoxy-9α,15α/β-dihydroxy-16-p-t-butyl                  phenoxy-17,20-                                                                tetranor-5-cis,13-trans-prostadienoic acid                      285  Example 142                                                                            dl-11-deoxy-9α,15α-dihydroxy-16-p-trifluoromethy                  l-                                                                            phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoic acid        286  Example 143                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-p-methoxy                  phenoxy-                                                                      17,20-tetranor-5-cis,13-trans-prostadienoic acid                287  Example 144                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-o-methoxy                  phenoxy-                                                                      17,20-tetranor-5-cis,13-trans-prostadienoic acid                288  Example 145                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-m-fluorop                  henoxy-17,20-                                                                 tetranor-5-cis,13-trans-prostadienoic acid                      289  Example 146                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-o-fluorop                  henoxy-17,20-                                                                 tetranor-5-cis,13-trans-prostadienoic acid                      290  Example 147                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-(3,4-dich                  lorophenoxy)-                                                                 17,20-tetranor-5-cis,13-trans-prostadienoic acid                291  Example 148                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-(2,5-dich                  lorophenoxy)-                                                                 17,20-tetranor-5-cis,13-trans-prostadienoic acid                292  Example 149                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-o-methylp                  henoxy-                                                                       17,20-tetranor-5-cis,13-trans-prostadienoic acid                293  Example 150                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-(2,3-dime                  thylphenoxy)-                                                                 17,20-tetranor-5-cis,13-trans-prostadienoic acid                294  Example 151                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-(3,5-dime                  thylphenoxy)-                                                                 17,20-tetranor-5-cis,13-trans-prostadienoic acid                295  Example 152                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-(2-chloro                  -4-methyl-                                                                    phenoxy)-17,20-tetranor-5-cis,13-trans-prostadienoic                          acid                                                            296  Example 153                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-m-dimethy                  lamino-                                                                       phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoic acid        297  Example 154                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-(1-naphth                  yloxy)-17,20-                                                                 tetranor-5-cis,13-trans-prostadienoic acid                      298  Example 155                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-(4-chloro                  -1-naphthyl-                                                                  oxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid           299  Example 156                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-(6-methyl                  -2-naphthyl-                                                                  oxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid           300  Example 157                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-(6-methox                  y-2-naphthyl-                                                                 oxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid           301  Example 158                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-(2,3-dich                  lorophenoxy)-                                                                 17,20-tetranor-5-cis,13-trans-prostadienoic acid                302  Example 159                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-(2,6-dich                  lorophenoxy)-                                                                 17,20-tetranor-5-cis,13-trans-prostadienoic acid                303  Example 160                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-(3,5-dich                  lorophenoxy)-                                                                 17,20-tetranor-5-cis,13-trans-prostadienoic acid                304  Example 161                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-(4-chloro                  -3-methyl-                                                                    phenoxy)-17,20-tetranor-5-cis,13-trans-prostadienoic                          acid                                                            305  Example 162                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-m-methoxy                  phenoxy-                                                                      17,20-tetranor-5-cis,13-trans-prostadienoic acid                306  Example 163                                                                            dl-11-deoxy-9α/β,15α/β-dihydroxy-16-(1                  -chloro-2-                                                                    naphthyloxy)-17,20-tetranor-5-cis,13-trans-prostadienoic                      acid                                                            307  Example 164                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-(5,6,7,8-                  tetranor-2-                                                                   naphthyloxy)-17,20-tetranor-5-cis,13-trans-prostadienoic                      acid                                                            308  Example 165                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-benzyloxy-                  17,20-tetra-                                                                  nor-5-cis,13-trans-prostadienoic acid                           309  Example 166                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-(2-naphthy                  loxy)-17,20-                                                                  tetranor-5-cis,13-trans-prostadienoic acid                      310  Example 167                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-p-chloroph                  enoxy-17,20-                                                                  tetranor-5-cis,13-trans-prostadienoic acid                      311  Example 168                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-m-chloroph                  enoxy-                                                                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                312  Example 169                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-o-chloroph                  enoxy-                                                                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                313  Example 170                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-(2,4-dichl                  orophenoxy)-                                                                  17,20-tetranor-5-cis,13-trans-prostadienoic acid                314  Example 171                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-p-fluoroph                  enoxy-                                                                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                315  Example 172                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-m-methylph                  enoxy-                                                                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                316  Example 173                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-p-trifluor                  omethyl-                                                                      phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoic                           acid                                                            317  Example 174                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-p-methoxyp                  henoxy-                                                                       17,20-tetranor-5-cis,13-trans-prostadienoic acid                318  Example 175                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-o-methoxyp                  henoxy-                                                                       17,20-tetranor-5-cis,13-trans-prostadienoic acid                319  Example 176                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-m-fluoroph                  enoxy-                                                                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                320  Example 177                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-o-fluoroph                  enoxy-                                                                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                321  Example 178                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-o-methylph                  enoxy-                                                                        17,20-tetranor-5-cis,13-trans-prostadienoic acid                322  Example 179                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-m-dimethyl                  amino-                                                                        phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoic                           acid                                                            323  Example 180                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-(1-naphthy                  loxy)-17,20-                                                                  tetranor-5-cis,13-trans-prostadienoic acid                      324  Example 181                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-(6-methoxy                  -2-naphthyl-                                                                  oxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid           325  Example 182                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-(2,3-dichl                  orophenoxy)-                                                                  17,20-tetranor-5-cis,13-trans-prostadienoic acid                326  Example 183                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-(3,5-dichl                  orophenoxy)-                                                                  17,20-tetranor-5-cis,13-trans-prostadienoic acid                327  Example 184                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-m-methoxyp                  henoxy-                                                                       17,20-tetranor-5-cis,13-trans-prostadienoic acid                328  Example 185                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-(5,6,7,8-t                  etrahydro-                                                                    2-naphthyloxy-17,20-tetranor-5-cis,13-trans-prosta-                           dienoic acid                                                    329  Example 186                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-phenoxy-17                  ,20-                                                                          tetranor-5-cis,13-trans-prostadienoic acid                      330  Example 187                                                                            dl-11-deoxy-15α-hydroxy-9-oxo-16-phenoxy-17,20-                         tetranor-13-trans-prostenoic acid                               331  Example 188                                                                            dl-11-deoxy-9α/β,15α/β-dihydroxy-16-p-                  methylphenoxy-                                                                17,20-tetranor-13-trans-prostenoic acid                         332  Example 189                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-m-methylp                  henoxy-                                                                       17,20-tetranor-13-trans-prostenoic acid                         333  Example 190                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-(3,5-dime                  thyl-                                                                         phenoxy)-17,20-tetranor-13-trans-prostenoic acid                334  Example 191                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-o-methoxyp                  henoxy-                                                                       17,20-tetranor-13-trans-prostenoic acid                         335  Example 192                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-o-methylp                  henoxy-                                                                       17,20-tetranor-13-trans-prostenoic acid                         336  Example 193                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-p-methoxyp                  henoxy-                                                                       17,20-tetranor-13-trans-prostenoic acid                         337  Example 194                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-m-dimethyl                  amino-                                                                        phenoxy-17,20-tetranor-13-trans-prostenoic acid                 338  Example 195                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-phenoxy-                   0                                                                             17,20-tetranor-prostanoic acid                                  339  Example 196                                                                            dl-11-deoxy-9α/β,15α/β-dihydroxy-16-p-                  methylphenoxy-                                                                17,20-tetranor-prostanoic acid                                  340  Example 197                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-m-methylp                  henoxy-                                                                       17,20-tetranor-prostanoic acid                                  341  Example 198                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-(3,5-dime                  thyl-                                                                         phenoxy)-17,20-tetranor-prostanoic acid                         342  Example 199                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-o-methoxyp                  henoxy-                                                                       17,20-tetranor-prostanoic acid                                  343  Example 200                                                                            dl-11-deoxy-9α/β,15α-dihydroxy-16-o-methylp                  henoxy-                                                                       17,20-tetranor-prostanoic acid                                  344  Example 201                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-p-methoxyp                  henoxy-                                                                       17,20-tetranor-prostanoic acid                                  345  Example 202                                                                            dl-11-deoxy-9α/β,15β-dihydroxy-16-m-dimethyl                  amino-                                                                        phenoxy-17,20-tetranor-prostanoic acid                          __________________________________________________________________________

EXAMPLE 346 Preparation ofdl-11-deoxy-15α-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid methyl ester

150 mg. ofdl-11-deoxy-15α-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid is dissolved in 10 ml. of ether, cooled to 0° C. and an etherealdiazomethane solution is added until a persistant yellow color isobserved. The excess diazomethane and solvent is removed under a streamof argon to provide the subject compound: λ max. 3400, 1740, 975 cm⁻¹.

EXAMPLES 347-356

The compounds of the following table when esterified with theappropriate diazoalkane by the procedure of Example 346 provide theproduct prostaglandin esters of the following table.

                                      TABLE 8                                     __________________________________________________________________________    Example                                                                            Starting acid                                                                        Diazoalkane                                                                          Product Prostaglandin Ester                                __________________________________________________________________________    347  Example 131                                                                          diazoethane                                                                          dl-11-deoxy-15α-hydroxy-9-oxo-16-benzyloxy-                             17,20-tetranor-5-cis,13-trans-prostadienoic                                   acid ethyl ester                                           348  Example 134                                                                          diazopropane                                                                         dl-11-deoxy-15α-hydroxy-9-oxo-16-m-chloro-                              phenoxy-17,20-tetranor-5-cis,13-trans-prosta-                                 dienoic acid propyl ester                                  349  Example 138                                                                          diazobutane                                                                          dl-11-deoxy-15α-hydroxy-9-oxo-16-p-fluoro-                              phenoxy-17,20-tetranor-5-cis,13-trans-prosta-                                 dienoic acid butyl ester                                   350  Example 142                                                                          diazopentane                                                                         dl-11-deoxy-15α-hydroxy-9-oxo-16-p-trifluoro-                           methylphenoxy-17,20-tetranor-5-cis,13-trans-                                  prostadienoic acid pentyl ester                            351  Example 163                                                                          diazohexane                                                                          dl-11-deoxy-15α/β-hydroxy-9-oxo-16-(1-chloro                       -                                                                             2-naphthyloxy)-17,20-tetranor-5-cis,13-                                       trans-prostadienoic acid hexyl ester                       352  Example 172                                                                          diasoheptane                                                                         dl-11-deoxy-15β-hydroxy-9-oxo-16-m-methyl-                               phenoxy-17,20-tetranor-5-cis,13-trans-prosta-                                 dienoic acid heptyl ester                                  353  Example 188                                                                          diazooctane                                                                          dl-11-deoxy-15α/β-hydroxy-9-oxo-16-p-methyl-                       O                                                                             phenoxy-17,20-tetranor-13-trans-prostenoic                                    acid octyl ester                                           354  Example 202                                                                          diazononane                                                                          dl-11-deoxy-9-oxo-15α-hydroxy-16-m-dinethyl-                            aminophenoxy-17,20-tetranor-prostanoic acid                                   nonyl ester                                                355  Example 207                                                                          diazodecane                                                                          dl-11-deoxy-9α,15α-dihydroxy-16-m-chloro-                         phenoxy-17,20-tetranor-5-cis,13-trans-prosta-                                 dienoic acid decyl ester                                   356  Example 316                                                                          diazomethane                                                                         dl-11-deoxy-9β-15β-dihydroxy-16-p-trifluoro-                        u                                                                             methylphenoxy-17,20-tetranor-5-cis,13-trans-                                  prostadienoic acid methyl ester                            __________________________________________________________________________

We claim:
 1. A compound selected from the group consisting of anoptically active compound of the formula: ##STR13## and a racemiccompound of that formula and the mirror image thereof; wherein R₁ ishydroxy or alkoxy having from 1 to 12 carbon atoms; R₂ is phenyl,naphthyl, 5,6,7,8-tetrahydronaphthyl, or 5,6,7,8-tetrahydronaphthylsubstituted with one or two groups selected from the group consisting ofhalogen, lower alkyl, lower alkoxy and n is an integer from 2 to 4,inclusive; X is a divalent moiety selected from the group consisting ofthose of the formulae: ##STR14## Y is a divalent moiety of the formulae:##STR15## the moiety of -C₅ -C₆ - is ethylene or cis-vinylene and themoiety -C₁₃ -C₁₄ - is ethylene or trans-vinylene with the proviso thatwhen -C₅ -C₆ - is cis-vinylene then -C₁₃ -C₁₄ - must be trans-vinylene;and the non-toxic cationic salts thereof when R₁ is hydroxy.
 2. Theenantiomer according to claim 1 wherein ##STR16## C₅ -C₆ iscis-vinylene, C₁₃ -C₁₄ is trans-vinylene, R₁ is hydroxy, R₂ iso-fluorophenoxy, and n is three;l-9-oxo-15α-hydroxy-16-o-fluorophenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid.
 3. The racemate according to claim 1 wherein ##STR17## C₅ -C₆ l iscis-vinylene, C₁₃ -C₁₄ l is trans-vinylene, R₁ is hydroxy, R₂ iso-fluorophenoxy, and n is three;dl-9-oxo-15α-hydroxy-16-o-fluorophenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid.
 4. The enantiomer according to claim 1 wherein ##STR18## C₅ -C₁₆is cis-vinylene, C₁₃ -C₁₄ is trans-vinylene, R₁ is hydroxy, R₂ isp-fluorophenoxy, and n is three,l-9-oxo-15β-hydroxy-16-p-fluorophenoxy-17,20-5-cis,13-trans-tetranor-prostadienoicacid.
 5. The racemate according to claim 1 wherein ##STR19## C₅ -C₆ iscis-vinylene, C₁₃ -C₁₄ is trans-vinylene, R₁ is hydroxy, R₂ isp-fluorophenoxy, and n is three,dl-9-oxo-15β-hydroxy-16-p-fluorophenoxy-17,20-5-cis,13-trans-tetranor-prostadienoicacid.
 6. The enantiomer according to claim 1 wherein ##STR20## C₅ -C₆ iscis-vinylene, C₁₃ -C₁₄ is trans-vinylene, R₁ is n-butyl, R₂ isp-fluorophenoxy, and n is three; l-butyl9-oxo-15α-hydroxy-16-p-fluorophenoxy-17,20-tetranor-5-cis,13-trans-prostadienoate.7. The racemate according to claim 1 wherein ##STR21## C₅ -C₆ iscis-vinylene, C₁₃ -C₁₄ is trans-vinylene, R₁ is n-butyl, R₂ isp-fluorophenoxy, and n is three; dl-butyl9-oxo-15α-hydroxy-16-p-fluorophenoxy-17,20-tetranor-5-cis,13-trans-prostadienoate.8. The enantiomer according to claim 1 wherein ##STR22## C₅ -C₆ iscis-vinylene, C₁₃ -C₁₄ is trans-vinylene, R₁ is hydroxy, R₂ iso-chlorophenoxy, and n is three;l-9-oxo-15α-hydroxy-16-o-chlorophenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid.
 9. The racemate according to claim 1 wherein ##STR23## C₅ -C₆ iscis-vinylene, C₁₃ -C₁₄ is trans-vinylene, R₁ is hydroxy, R₂ iso-chlorophenoxy, and n is three;dl-9-oxo-15α-hydroxy-16-o-chlorophenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid.
 10. The enantiomer according to claim 1 wherein ##STR24## C₅ -C₆is cis-vinylene, C₁₃ -C₁₄ is trans-vinylene, R₁ is hydroxy, R₂ ism-chlorophenoxy, and n isthree;l-9-oxo-15α-hydroxy-16-m-chlorophenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid.
 11. The racemate according to claim 1 wherein ##STR25## C₅ -C₆ iscis-vinylene, C₁₃ -C₁₄ is trans-vinylene, R₁ is hydroxy, R₂ ism-chlorophenoxy, and n is three;dl-9-oxo-15α-hydroxy-16-m-chlorophenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid.
 12. The enantiomer according to claim 1 wherein ##STR26## C₅ -C₆is cis-vinylene, C₁₃ -C₁₄ is trans-vinylene, R₁ is n-propoxy, R₂ ism-chlorophenoxy, and n is three; l-propyl9-oxo-15α-hydroxy-5-cis,13-trans-16-m-chlorophenoxy-17,20-tetranor-prostadienoate.13. The racemate according to claim 1 wherein ##STR27## C₅ -C₆ iscis-vinylene, C₁₃ -C₁₄ is trans-vinylene, R₁ is n-propoxy, R₂ ism-chlorophenoxy, and n is three; dl-propyl9-oxo-15α-hydroxy-5-cis,13-trans-16-m-chlorophenoxy-17,20-tetranor-prostadienoate.14. The enantiomer according to claim 1 wherein ##STR28## C₅ -C₆ iscis-vinylene, C₁₃ -C₁₄ is trans-vinylene, R₁ is hydroxy, R₂ ism-chlorophenoxy, and n is three;l-9-oxo-15β-hydroxy-16-m-chlorophenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid.
 15. The racemate according to claim 1 wherein ##STR29## C₅ -C₆ iscis-vinylene, C₁₃ -C₁₄ is trans-vinylene, R₁ is hydroxy, R₂ ism-chlorophenoxy, and n is three;dl-9-oxo-15β-hydroxy-16-m-chlorophenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid.
 16. The enantiomer according to claim 1 wherein ##STR30## C₅ -C₆is cis-vinylene, C₁₃ -C₁₄ is trans-vinylene, R₁ is hydroxy, R₂ isp-chlorophenoxy, and n is three;l-9-oxo-15α-hydroxy-16-p-chlorophenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid.
 17. The racemate according to claim 1 wherein ##STR31## C₅ -C₆ iscis-vinylene, C₁₃ -C₁₄ is trans-vinylene, R₁ is hydroxy, R₂ isp-chlorophenoxy, and n is three;dl-9-oxo-15α-hydroxy-16-p-chlorophenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid.
 18. The enantiomer according to claim 1 wherein ##STR32## C₅ -C₆is cis-vinylene, C₁₃ -C₁₄ is trans-vinylene, R₁ is hydroxy, R₂ isp-trifluoromethylphenoxy, and n is three;l-9-oxo-15α-hydroxy-16-p-trifluoromethylphenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid.
 19. The racemate according to claim 1 wherein ##STR33## C₅ -C₆ iscis-vinylene, C₁₃ -C₁₄ is trans-vinylene, R₁ is hydroxy, R₂ isp-trifluoromethylphenoxy, and n is three;dl-9-oxo-15α-hydroxy-16-p-trifluoromethylphenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid.
 20. The enantiomer according to claim 1 wherein ##STR34## C₅ -C₆is cis-vinylene, C₁₃ -C₁₄ is trans-vinylene, R₁ is n-pentyloxy, R₂ isp-trifluoromethylphenoxy, and n is three; l-pentyl9-oxo-15α-hydroxy-16-p-trifluoromethylphenoxy-17,20-tetranor-5-cis,13-trans-prostadienoate.21. The racemate according to claim 1 wherein ##STR35## C₅ -C₆ iscis-vinylene, C₁₃ -C₁₄ is trans-vinylene, R₁ is n-pentyloxy, R₂ isp-trifluoromethylphenoxy, and n is three; dl-pentyl9-oxo-15α-hydroxy-16-p-trifluoromethylphenoxy-17,20-tetranor-5-cis,13-trans-prostadienoate.22. The enantiomer according to claim 1 wherein ##STR36## C₅ -C₆ iscis-vinylene, C₁₃ -C₁₄ is trans-vinylene, R₁ is hydroxy, R₂ ism-trifluoromethylphenoxy, and n is three;l-9-oxo-15β-hydroxy-16-m-trifluoromethylphenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid.
 23. The racemate according to claim 1 wherein ##STR37## C₅ -C₆ iscis-vinylene, C₁₃ -C₁₄ is trans-vinylene, R₁ is hydroxy, R₂ L ism-trifluoromethylphenoxy, and n is three; dl-9-oxo-15β-hydroxy-16-m-trifluoromethylphenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid.
 24. The compound according to claim 1 wherein n is 3, C₁₃ -C₁₄ istrans-vinylene, and C₆ -C₅ is cis-vinylene.
 25. The compound accordingto claim 24 wherein C₆ -C₅ is ethylene and C₁₃ -C₁₄ is trans-vinylene.26. The compound according to claim 24 wherein C₆ -C₅ is cis-vinyleneand C₁₃ -C₁₄ is trans-vinylene.
 27. The compound according to claim 1wherein R₂ is phenyl substituted with one or two groups selected fromthe group consisting of halogen, lower alkyl and lower alkoxy.
 28. Thecompound according to claim 27 wherein R₁ is hydroxy.
 29. The compoundaccording to claim 27 wherein R₁ is alkoxy having 1 to 12 carbon atoms.30. The compound according to claim 1 wherein n is
 3. 31. The compoundaccording to claim 27 wherein n is
 3. 32. The racemic compound accordingto claim 26,dl-11-deoxy-15α-hydroxy-9-oxo-16-phenoxy-17,20-tretanor-5-cis,13-transprostadienoic acid and the enantiomerl-11-deoxy-15α-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,13-transprostadienoicacid.
 33. The racemic compound according to claim 26,dl-11-deoxy-15α-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid methyl ester, and the enantiomerl-11-deoxy-15α-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoicacid methyl ester.
 34. A compound selected from the group consisting ofan optically active compound of the formula ##STR38## and a racemiccompound of that formula and the mirror image thereof, wherein R₁ ishydroxy or alkoxy having from 1 to 12 carbon atoms; R₂ is phenyl,benzyl, naphthyl, or 5,6,7,8-tetrahydronaphthyl or R₂ is phenyl, benzyl,naphthyl or 5,6,7,8-tetrahydronaphthyl wherein each of said substituentsincludes one or more substituents selected from the group consisting ofhalogen, lower alkyl or lower alkoxy; n is an integer from 2 to 4, X isa divalent moiety selected from the group consisting of those of theformulae: ##STR39## C₆ -C₅ is ethylene or trans-vinylene and C₁₃ -C₁₄ isethylene or trans-vinylene, with a proviso that when C₆ -C₅ iscis-vinylene then C₁₃ -C₁₄ must be trans-vinylene; and the non-toxiccationic salts thereof when R is hydroxy.
 35. The compound according toclaim 34 wherein R₂ is selected from the group consisting of phenyl andphenyl substituted with one or two substituent groups selected from thegroup consisting of halogen, lower alkyl and lower alkoxy.
 36. Thecompound according to claim 34 wherein R₂ is phenyl.
 37. The compoundaccording to claims 35 or 36 wherein C₆ -C₅ is ethylene and C₁₃ -C₁₄ istrans-vinylene.
 38. The compound according to claim 37 wherein n is 3.39. The compound according to claim 34 wherein R₂ is selected from thegroup consisting of p-methylphenyl, m-methylphenyl, 3,5-dimethylphenyl,o-methoxyphenoxy, o-methylphenyl, and o-ethylphenyl.
 40. The racemateaccording to claim 37,dl-15α-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-13-trans-prostenoic acidor its mirror image.
 41. The enantiomer according to claim 37,15α-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-13-trans-prostenoic acid orits mirror image.
 42. The enantiomer according to claim 37,15α-hydroxy-9-oxo-16-p-methylphenoxy-17,20-tetranor-13-trans-prostenoicacid or its mirror image.
 43. The racemate according to claim 37,dl-15α-hydroxy-9-oxo-16-p-methylphenoxy-17,20-tetranor-13-trans-prostenoicacid.
 44. The enantiomer according to claim 37,15α-hydroxy-9-oxo-16-m-methylphenoxy-17,20-tetranor-13-trans-prostenoicacid or its mirror image.
 45. The racemate according to claim 37,dl-15α-hydroxy-9-oxo-16-m-methylphenoxy-17,20-tetranor-13-trans-prostenoicacid.
 46. The enantiomer according to claim 37,15α-hydroxy-9-oxo-16-(3,5-dimethylphenoxy)-17,20-tetranor-13-trans-prostenoicacid or its mirror image.
 47. The racemate according to claim 37,dl-15α-hydroxy-9-oxo-16-(3,5-dimethylphenoxy)-17,20-tetranor-13-trans-prostenoicacid.
 48. The enantiomer according to claim 37,15β-hydroxy-9-oxo-16-o-methyoxyphenoxy-17,20-tetranor-13-trans-prostenoicacid or its mirror image.
 49. The racemate according to claim 37,dl-15β-hydroxy-9-oxo-16-o-methoxyphenoxy-17,20-tetranor-13-trans-prostenoicacid.
 50. The enantiomer according to claim 37,15α-hydroxy-9-oxo-16-o-methylphenoxy-17,20-tetranor-13-trans-acid or itsmirror image.
 51. The racemate according to claim 37,dl-15-α-hydroxy-9-oxo-16-o-ethylphenoxy-17,20-tetranor-13-trans-prostenoicacid.
 52. The enantiomer according to claim 37,15β-hydroxy-9-oxo-16-p-methoxyphenoxy-17,20-tetranor-13-trans-prostenoicacid or its mirror image.
 53. The racemate according to claim 37,dl-15β-hydroxy-9-oxo-16-p-methoxyphenoxy-17,20-tetranor-13-trans-prostenoicacid.
 54. The enantiomer according to claim 37,15β-hydroxy-9-oxo-16-m-dimethylamino-phenoxy-17,20-tetranor-13-trans-prostenoicacid or its mirror image.
 55. The racemate according to claim 37,dl-15β-hydroxy-9-oxo-16-m-dimethylamino-phenoxy-17,20-tetranor-13-trans-prostenoicacid.
 56. The enantiomer according to claim 37,15α-hydroxy-9-oxo-16-p-methylphenoxy-17,20-tetranor-13-trans-prostenoicacid octyl ester or its mirror image.
 57. The racemate according toclaim 37,dl-15α-hydroxy-9-oxo-16-p-methylphenoxy-17,20-tetranor-13-trans-prostenoicacid octyl ester.